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OC-0310: Hypofractionated radiotherapy (RT) boost for children with Ependymoma and a measurable residue after surgery
3rd ESTRO Forum 2015 F. Tensaouti1, A. Ducassou2, S. Liceaga1, J.A. Lotterie3, A. Sevely4, P. Peran1, I. Berry4, S. Ken2, P. Celsis1, A. Laprie2 1 INSERM, UMR 825, Toulouse, France 2 Institut du Cancer de Toulouse, Radiotherapy, Toulouse, France 3 CHU Toulouse, Radiotherapy, Toulouse, France 4 CHU Toulouse, Radiology, Toulouse, France Purpose/Objective: Ependymoma is the third most common primary brain tumor in children. Radiotherapy is systematically delivered after surgery. However, more than a third of children experience relapse locally or around the resection cavity wall. One important factor influencing clinical outcome after radiotherapy is the reduced oxygen levels (hypoxia). Major noninvasive technique suggested as capable of monitoring tumour hypoxia involves MR, and includes both perfusion MRI (by dynamic contrast-enhanced MRI, DCE) and diffusionweighted imaging (DWI). The aim of this study was to investigate if DCE or DWI MRI can predict radiotherapy outcome in pediatric ependymoma by identification of significant hypoxic subvolumes of tumors related to treatment outcomes and that resistance resulting from this hypoxia can be overcome by increasing radiation dose. Materials and Methods: 197 patients were included in this national retrospective study, performed in 11 french reference centers for pediatric radiation oncology. All patients underwent surgical resection and postoperative radiochimiotherapy. Imaging data from 93 patients could be retrieved. Among them eleven patients had DCE MRI and fifteen had DWI MRI at pre radiotherapy exam. All image analyses were completed using an in-house software package: Sisyphe. For each patient, the resection cavity was delineated on the post contrast T1WI. The resulting Region of interest (ROI) was mapped to the coregistered CBV and ADC map. An histogram analysis was done to determine for both CBV and ADC the best fitting of the data hitogramm with 2 or 3 Gaussian functions. According to the fitting results, the cavity ROI was then partitioned into 2 or 3 spatial subvolumes using an automatic clustering method (Isodata algorithm). Each subvolume with the lower CBV or lower ADC was normalized to the ROI volume and evaluated for its association with outcome. Results: The percentage of the subvolumes with low ADC, was not signi?cantly different between the patients with Local Failure (LF) and local control (LC) (p = 0.9). The percentage of the subvolumes with low CBV, were signi?cantly greater, in the patients with LF than with LC ( p = 0.025). The ROC analysis indicates that for a subvolume of 69 % of the volume ROI with low CBV had greater speci?city for prediction of local failure (specificity =80%, sensibility=100%). Conclusions: In our study perfusion MRI was a predictive factor of radiotherapy outcome in pediatric ependymoma. This is a promising finding as radio resistance resulting from hypoperfusion and consequent hypoxia could be overcome by increasing radiation dose to the poorly perfused defined subvolumes. Confirmation of our imaging data is in progress with completion of our database that will allow to present our final results to the meeting. OC-0309 Role of age, grade and RT dose on outcome of 177 ependymoma - 13 years experience of Child's cancer French Society A. Ducassou1, X. Murraciole2, L. Chaltiel3, S. Bolle4, L. Claude5, V. Bernier6, B. Coche-Dequeant7, S. Supiot8, A.
S155 Huchet9, C. Kerr10, T.D. Nguyen11, C. Alapetite12, F. Tensaouti13, S. Liceaga13, T. Filleron3, A. Laprie1 1 Institut Claudius Regaud, radiotherapy, Toulouse, France 2 CHU La Timone, radiotherapy, Marseille, France 3 Institut Claudius Regaud, biostatistics, Toulouse, France 4 Gustave Roussy, Radiotherapy, Villejuif, France 5 Centre Léon Bérard, Radiotherapy, Lyon, France 6 Centre Alexis Vautrin, Radiotherapy, nancy, France 7 Centre Oscar Lambret, Radiotherapy, Lille, France 8 ICO, Radiotherapy, Nantes, France 9 CHU Bordeaux, Radiotherapy, Bordeaux, France 10 Centre Val d'Aurelle, Radiotherapy, montpellier, France 11 CLLC, Radiotherapy, Reims, France 12 institut Curie, Radiotherapy, Paris, France 13 INSERM, UMR 825 neuroimaging, Toulouse, France Purpose/Objective: to investigate the influence on Event free survival ( EFS) and overall survival ( OS ) of main characteristics of patients, disease and treatments for pediatric patients with localised ependymoma in a national cohort Materials and Methods: A total of 177 patients with newly diagnosed intracranial ependymoma were treated with adjuvant Radiation therapy (RT) in the 11 French major radiation oncology centers between January 2000 and December 2013. Clinical data were retrospectively gathered on a web-based national database between March and October 2014. Results: Location was posterior fossa in 77%, supratentorial in 23 %. Anaplastic features were present in 56% of patients. The extent of resection was characterized as gross-total in 86% patients and subtotal in 14%. The median dose to the primary site was 59.4 Gy, 37% of patients received a dose ≤54 Gy. Fifty-one patients received pre-RT chemotherapy. RT was 3D conformal in 107 patients, IMRT in 60 (of which 18 tomotherapy) and protontherapy in 10. With a median follow up time of 43.1 months from the start of RT (95%CI (33,5-52.6)), the 3-years local relapse-free survival (LRFS) was 67,8%. Recurrences after RT occurred in 73 patients (41%) and were mainly local (strictly local in 62% of recurrences, local and distant in 7% and strictly distant in 25%). The RT dose significantly influenced overall survival (OS) and event-free survival (EFS) after RT. The estimated 3-year OS and EFS rates were respectively 90 % and 67% for patients who received a dose > 54Gy compared with 79% and 52% for patients who received a dose ≤54 Gy (respectively p= 0.008 and p=0.02). OS and EFS at 3 years were significantly improved for patients older than 3 years of age at the initiation of RT (92 and 68%) compared to children younger than 3 years (71 and 43%) (p=0.0007 and p=0.0001). EFS at 3 years was greater in grade 1-2 (74%) than in grade 3-4 (53%) (p=0.004), OS was also greater in grade 1-2 (97%) than grade 3-4 (81%) but this was not statistically significant. There was no significant difference in OS or EFS regarding the quality of surgery, the use of chemotherapy or the technique of radiotherapy. Conclusions: This large multicentric French cohort confirms that a dose > 54 Gy improved survival in localised cerebral ependymoma. Age younger than 3 years at initiation of RT and grade 3-4 were significant prognostic factors of worse outcome. OC-0310 Hypofractionated radiotherapy (RT) boost for children with Ependymoma and a measurable residue after surgery
S156 L. Gandola1, E. Pecori1, G. Scarzello2, S. Barra3, M. Mascarin4, S. Scoccianti5, B. Diletto6, A. Mussano7, M.L. Garré8, I. Sardi9, S. Meroni10, V. Biassoni11, E. Pignoli10, F. Giangaspero12, M. Massimino13 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy Unit, Milan, Italy 2 Istituto Oncologico del Veneto, Radiotherapy Unit, Padova, Italy 3 IRCCS Azienda Ospedaliera Universitaria San Martino - IST, Radiotherapy Unit, Genova, Italy 4 C.R.O. Aviano, Radiotherapy Unit, Aviano, Italy 5 AOU Careggi, Radiotherapy Unit, Firenze, Italy 6 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy Unit, Milano, Italy 7 Ospedaliera O.I.R.M. S. Anna, Radiotherapy Unit, Torino, Italy 8 Istituto G. Gaslini, Pediatric Neuro-Oncology Unit, Genova, Italy 9 Ospedale Pediatrico Meyer, Pediatric Neuro-Oncology Unit, Firenze, Italy 10 Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Physics Unit, Milano, Italy 11 Fondazione IRCCS Istituto Nazionale dei Tumori, Pediatric Oncology Unit, Milano, Italy 12 Università La Sapienza, Pathology Unit, Roma, Italy 13 Fondazione IRCCS Istituto Nazionale dei Tumori, Pediatric Oncology Unit, Roma, Italy Purpose/Objective: To evaluate feasibility in a multicentric setting and clinical results of a RT boost for children with Ependymoma and measurable residual disease after first line or second look surgery. Materials and Methods: The second AIEOP (Italian Association of Pediatric Hematology and Oncology) protocol for childhood ependymoma opened in 2003. After centralized pathological review, children were stratified to receive: 1) 3D conformal RT or IMRT, 59.4 Gy/33 fractions, to the tumor bed in case of complete resection and grade II tumor; 2) same RT followed by four cycles of VEC chemotherapy in case of complete resection and anaplastic ependymoma; 3) VECx4, second look surgery whenever feasible, local RT as in 1) followed by a stereotactic hypofractionated (8 Gy/2 fractions) boost to the residue still measurable after previous treatments. Results: From 2003, 143 children entered the study (median follow-up 60 months). In 24 children (median age 4,5 years, 15 grade II, 20 infratentorial), out of 46 with residue after first surgery, second look wasn't feasible or incomplete and thus received VEC and 59.4 Gy to the tumor bed plus 8 Gy to the gross residue. 15/24 children are alive without progression at a median of 51 months (range 11-120 mos) from diagnosis, 5/6 died of local progression at a median of 20 months, and 3 relapsed distantly, 17-23 months from diagnosis, and have died. No iatrogenic death or major toxicity occurred. 4 children, irradiated with Tomotherapy, developed radiation related MRI changes regressing with steroids within 8 months. In the 46 children with residual disease, 3 and 5 years PFS was 64% and 55%, and OS 80% and 68% respectively. 3 and 5-year survival free from local relapse was 71% and 64% respectively. 5 year-EFS for children receiving the RT boost was 57%. Conclusions: Hypofractionated RT boost was feasible and contributed to obtain durable local control in 15/24 children with measurable residue after first line or second look surgery. An aggressive and integrated local treatment strategy, multiple surgeries and RT including an hypofractionated boost in case of residual disease, is required to improve outcome in children with Ependymoma.
3rd ESTRO Forum 2015 This background will be the basis of the next opening SIOP (Société International d'Oncologie Pediatrique) trial for Ependymoma.
Symposium with Proffered Papers: SBRT: What is the evidence?
SP-0311 Treating primary tumors with SBRT M. Dahele1 1 VU University Medical Center, Amsterdam, The Netherlands
Radiation
Oncology,
Stereotactic body radiotherapy (SBRT) frequently involves the accurate delivery of a few large fractions to a relatively welldefined target. The favorable anti-tumor characteristics of large fractions needs to be balanced against the fact that they are often poorly tolerated by normal organs. Although this means that SBRT is not possible in all clinical situations, in others the risks can be managed in a variety of ways including the use of planning and delivery techniques that simultaneously facilitate target coverage and organ at risk sparing. While the application of extremely hypofractionated radiotherapy to the radical treatment of primary tumors is not new, current interest coincides with the widespread availability of advanced radiotherapy systems. Nonetheless, the successful paradigm of using SBRT to treat peripheral, early-stage lung cancer has yet to be replicated in other clinical scenarios. Against this background the present talk aims to briefly outline the essential features of SBRT; describe the historical aspects of extreme hypofractionation for radical treatments; succinctly review the current literature on SBRT for treating primary tumors; discuss some of the challenges in using SBRT for this indication; and touch on future perspectives. SP-0312 Is SBRT a best tool in the treatment of oligometastatic disease? U. Ricardi1 1 Universita di Torino, Radiation Oncology, Torino, Italy Metastases account for approximately 80–90% of cancer deaths. Systemic therapies (either cytotoxic chemotherapy or targeted agents), the cornerstone for treatment in metastatic disease, are rather than curative. Therefore, novel therapies for the treatment of patients with metastatic cancer are needed. In 1995, Hellmann and Weichselbaum coined the term “oligometastases” to describe a less-advanced (or “intermediate”) state of metastatic disease, peculiarly situated between locoregionally-confined and widelymetastatic cancer. In this paradigm, a limited burden of metastatic disease may be amenable to potentially curative local therapies. Stereotactic Body RadioTherapy (SBRT), which is also referred to as Stereotactic Ablative Radiotherapy (SABR), is a form of high-precision radiotherapy, tipically delivered in one to 8 fractions, commonly using fraction sizes of 7.5 Gy or more. SBRT allows for target dose-escalation (thus increasing tumor control), while minimizing normal tissue exposure (thus minimizing the toxicity risk). When compared to surgery, SBRT has the theoretical advantage to be less invasive and more effective, because of lower morbidity rates, lower costs and the potential for delivering ablative treatments on an outpatient basis.
S155 Huchet9, C. Kerr10, T.D. Nguyen11, C. Alapetite12, F. Tensaouti13, S. Liceaga13, T. Filleron3, A. Laprie1 1 Institut Claudius Regaud, radiotherapy, Toulouse, France 2 CHU La Timone, radiotherapy, Marseille, France 3 Institut Claudius Regaud, biostatistics, Toulouse, France 4 Gustave Roussy, Radiotherapy, Villejuif, France 5 Centre Léon Bérard, Radiotherapy, Lyon, France 6 Centre Alexis Vautrin, Radiotherapy, nancy, France 7 Centre Oscar Lambret, Radiotherapy, Lille, France 8 ICO, Radiotherapy, Nantes, France 9 CHU Bordeaux, Radiotherapy, Bordeaux, France 10 Centre Val d'Aurelle, Radiotherapy, montpellier, France 11 CLLC, Radiotherapy, Reims, France 12 institut Curie, Radiotherapy, Paris, France 13 INSERM, UMR 825 neuroimaging, Toulouse, France Purpose/Objective: to investigate the influence on Event free survival ( EFS) and overall survival ( OS ) of main characteristics of patients, disease and treatments for pediatric patients with localised ependymoma in a national cohort Materials and Methods: A total of 177 patients with newly diagnosed intracranial ependymoma were treated with adjuvant Radiation therapy (RT) in the 11 French major radiation oncology centers between January 2000 and December 2013. Clinical data were retrospectively gathered on a web-based national database between March and October 2014. Results: Location was posterior fossa in 77%, supratentorial in 23 %. Anaplastic features were present in 56% of patients. The extent of resection was characterized as gross-total in 86% patients and subtotal in 14%. The median dose to the primary site was 59.4 Gy, 37% of patients received a dose ≤54 Gy. Fifty-one patients received pre-RT chemotherapy. RT was 3D conformal in 107 patients, IMRT in 60 (of which 18 tomotherapy) and protontherapy in 10. With a median follow up time of 43.1 months from the start of RT (95%CI (33,5-52.6)), the 3-years local relapse-free survival (LRFS) was 67,8%. Recurrences after RT occurred in 73 patients (41%) and were mainly local (strictly local in 62% of recurrences, local and distant in 7% and strictly distant in 25%). The RT dose significantly influenced overall survival (OS) and event-free survival (EFS) after RT. The estimated 3-year OS and EFS rates were respectively 90 % and 67% for patients who received a dose > 54Gy compared with 79% and 52% for patients who received a dose ≤54 Gy (respectively p= 0.008 and p=0.02). OS and EFS at 3 years were significantly improved for patients older than 3 years of age at the initiation of RT (92 and 68%) compared to children younger than 3 years (71 and 43%) (p=0.0007 and p=0.0001). EFS at 3 years was greater in grade 1-2 (74%) than in grade 3-4 (53%) (p=0.004), OS was also greater in grade 1-2 (97%) than grade 3-4 (81%) but this was not statistically significant. There was no significant difference in OS or EFS regarding the quality of surgery, the use of chemotherapy or the technique of radiotherapy. Conclusions: This large multicentric French cohort confirms that a dose > 54 Gy improved survival in localised cerebral ependymoma. Age younger than 3 years at initiation of RT and grade 3-4 were significant prognostic factors of worse outcome. OC-0310 Hypofractionated radiotherapy (RT) boost for children with Ependymoma and a measurable residue after surgery
S156 L. Gandola1, E. Pecori1, G. Scarzello2, S. Barra3, M. Mascarin4, S. Scoccianti5, B. Diletto6, A. Mussano7, M.L. Garré8, I. Sardi9, S. Meroni10, V. Biassoni11, E. Pignoli10, F. Giangaspero12, M. Massimino13 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy Unit, Milan, Italy 2 Istituto Oncologico del Veneto, Radiotherapy Unit, Padova, Italy 3 IRCCS Azienda Ospedaliera Universitaria San Martino - IST, Radiotherapy Unit, Genova, Italy 4 C.R.O. Aviano, Radiotherapy Unit, Aviano, Italy 5 AOU Careggi, Radiotherapy Unit, Firenze, Italy 6 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy Unit, Milano, Italy 7 Ospedaliera O.I.R.M. S. Anna, Radiotherapy Unit, Torino, Italy 8 Istituto G. Gaslini, Pediatric Neuro-Oncology Unit, Genova, Italy 9 Ospedale Pediatrico Meyer, Pediatric Neuro-Oncology Unit, Firenze, Italy 10 Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Physics Unit, Milano, Italy 11 Fondazione IRCCS Istituto Nazionale dei Tumori, Pediatric Oncology Unit, Milano, Italy 12 Università La Sapienza, Pathology Unit, Roma, Italy 13 Fondazione IRCCS Istituto Nazionale dei Tumori, Pediatric Oncology Unit, Roma, Italy Purpose/Objective: To evaluate feasibility in a multicentric setting and clinical results of a RT boost for children with Ependymoma and measurable residual disease after first line or second look surgery. Materials and Methods: The second AIEOP (Italian Association of Pediatric Hematology and Oncology) protocol for childhood ependymoma opened in 2003. After centralized pathological review, children were stratified to receive: 1) 3D conformal RT or IMRT, 59.4 Gy/33 fractions, to the tumor bed in case of complete resection and grade II tumor; 2) same RT followed by four cycles of VEC chemotherapy in case of complete resection and anaplastic ependymoma; 3) VECx4, second look surgery whenever feasible, local RT as in 1) followed by a stereotactic hypofractionated (8 Gy/2 fractions) boost to the residue still measurable after previous treatments. Results: From 2003, 143 children entered the study (median follow-up 60 months). In 24 children (median age 4,5 years, 15 grade II, 20 infratentorial), out of 46 with residue after first surgery, second look wasn't feasible or incomplete and thus received VEC and 59.4 Gy to the tumor bed plus 8 Gy to the gross residue. 15/24 children are alive without progression at a median of 51 months (range 11-120 mos) from diagnosis, 5/6 died of local progression at a median of 20 months, and 3 relapsed distantly, 17-23 months from diagnosis, and have died. No iatrogenic death or major toxicity occurred. 4 children, irradiated with Tomotherapy, developed radiation related MRI changes regressing with steroids within 8 months. In the 46 children with residual disease, 3 and 5 years PFS was 64% and 55%, and OS 80% and 68% respectively. 3 and 5-year survival free from local relapse was 71% and 64% respectively. 5 year-EFS for children receiving the RT boost was 57%. Conclusions: Hypofractionated RT boost was feasible and contributed to obtain durable local control in 15/24 children with measurable residue after first line or second look surgery. An aggressive and integrated local treatment strategy, multiple surgeries and RT including an hypofractionated boost in case of residual disease, is required to improve outcome in children with Ependymoma.
3rd ESTRO Forum 2015 This background will be the basis of the next opening SIOP (Société International d'Oncologie Pediatrique) trial for Ependymoma.
Symposium with Proffered Papers: SBRT: What is the evidence?
SP-0311 Treating primary tumors with SBRT M. Dahele1 1 VU University Medical Center, Amsterdam, The Netherlands
Radiation
Oncology,
Stereotactic body radiotherapy (SBRT) frequently involves the accurate delivery of a few large fractions to a relatively welldefined target. The favorable anti-tumor characteristics of large fractions needs to be balanced against the fact that they are often poorly tolerated by normal organs. Although this means that SBRT is not possible in all clinical situations, in others the risks can be managed in a variety of ways including the use of planning and delivery techniques that simultaneously facilitate target coverage and organ at risk sparing. While the application of extremely hypofractionated radiotherapy to the radical treatment of primary tumors is not new, current interest coincides with the widespread availability of advanced radiotherapy systems. Nonetheless, the successful paradigm of using SBRT to treat peripheral, early-stage lung cancer has yet to be replicated in other clinical scenarios. Against this background the present talk aims to briefly outline the essential features of SBRT; describe the historical aspects of extreme hypofractionation for radical treatments; succinctly review the current literature on SBRT for treating primary tumors; discuss some of the challenges in using SBRT for this indication; and touch on future perspectives. SP-0312 Is SBRT a best tool in the treatment of oligometastatic disease? U. Ricardi1 1 Universita di Torino, Radiation Oncology, Torino, Italy Metastases account for approximately 80–90% of cancer deaths. Systemic therapies (either cytotoxic chemotherapy or targeted agents), the cornerstone for treatment in metastatic disease, are rather than curative. Therefore, novel therapies for the treatment of patients with metastatic cancer are needed. In 1995, Hellmann and Weichselbaum coined the term “oligometastases” to describe a less-advanced (or “intermediate”) state of metastatic disease, peculiarly situated between locoregionally-confined and widelymetastatic cancer. In this paradigm, a limited burden of metastatic disease may be amenable to potentially curative local therapies. Stereotactic Body RadioTherapy (SBRT), which is also referred to as Stereotactic Ablative Radiotherapy (SABR), is a form of high-precision radiotherapy, tipically delivered in one to 8 fractions, commonly using fraction sizes of 7.5 Gy or more. SBRT allows for target dose-escalation (thus increasing tumor control), while minimizing normal tissue exposure (thus minimizing the toxicity risk). When compared to surgery, SBRT has the theoretical advantage to be less invasive and more effective, because of lower morbidity rates, lower costs and the potential for delivering ablative treatments on an outpatient basis.