EP-1053: Efficacy and toxicity of chemo-radiotherapy in Hodgkinís lymphoma: A single institution experience

ESTRO 33, 2014 Results: Treatment outcome and brain necrosis was evaluated by brainMRI and neurological status according to clinical and MacDonald/RANO criteria. Doses to GTV, PTV and relevant organs at risk(OARs): Brainstem, Chiasm, Optic Nerves, Brain) were examined. Radiographic response criteria aftrer Re-RT were not defined. A radionecrosis diagnosed by radiographic imaging was shown in 2 patients 9 and11 months after re-RT . The median follow-up time was 6.9 months (range 2.8-20months). Overall Survival (OS) was measured from the 1st day of re-RT until death. Median OS from re-RTwas 10 months (range 6.1-19.2 months) for all patients. Median Progression Free Survival (PFS) was 4.3 months (range 2.8-15) Conclusions: The above data clearly indicate that re-RT is feasible with an acceptable toxicity profile and has become a realistic treatment option for recurrent GBM patients. EP-1051 Stereotactic radiosurgery and stereotactic radiation therapy in the management of brain metastases J. McCarthy1, A. O'Donovan1 1 Discipline of Radiation Therapy, School of Medicine Trinity Centre for Health Sciences, Dublin, Ireland Republic of Purpose/Objective: In recent years, there has been a shift in the treatment paradigm of brain metastases (BM). Whole brain radiation therapy (WBRT), which was the mainstay of metastatic brain tumour therapy for decades, has been replaced with more advanced therapies, such as stereotactic radiosurgery (SRS) and stereotactic radiation therapy (SRT). Practice guidelines have been published regarding the role of SRS in the management of BM, but little evidence exists to demonstrate how these guidelines are being implemented. Furthermore, the use of SRT has been shown to have a therapeutic advantage in selected patients with BM, however no guidelines have been published to determine its optimal role. This study investigated the clinical implementation of SRS and SRT in the management of BM across Europe and North America. Materials and Methods: An online questionnaire was distributed to approximately 500 radiation oncologists and members of the multidisciplinary team involved in the treatment of BM using SRS. The questionnaire consisted of seven sections: demographics, inclusion criteria, the role of WBRT, target volume delineation, treatment planning and delivery of SRS, treatment planning and delivery of SRT, and the current role of SRT. Participants were identified through internet searches, ASTRO and ESTRO membership directories, and published literature in the area. Results: All evaluable respondents (n=73) performed SRS, and 67% of respondents performed SRT in the management of BM. Considerable variation was observed in the implementation of SRS and SRT, both among respondents themselves, and with respect to the literature. The use of SRS is widely advocated, even in the presence of poor prognostic factors. SRT was employed by 67% of respondents in the management of BM, however there was no consensus on the optimal dose and fractionation schedule employed. Conclusions: Although extensive research has been carried out to determine the optimal role of SRS in the management of BM, considerable variation exists on its clinical implementation. Variation on the implementation of SRT is also evident, and the publication of guidelines is warranted, given the level of variation that exists.

S3 incomplete resection. Residual disease was defined as the presence of a nodular area > 1 cm with contrast enhancement in the T1 weighted sequences. The site of recurrence was defined as 'central' when > 80% of the recurrent mass was located within the volume encompassed by 95% isodose, 'marginal' when < 80% but > 20% of the recurrence was located within the volume encompassed by 95% isodose, and out of the field when < 20% was located within the volume encompassed by 95% isodose. In all other cases recurrences were defined as outside the radiation field. Results: At a median follow up of 9 months (range 2-46), 46 pts presented a recurrence (82,1%). Median time from the start of postoperative RT to the diagnosis of recurrence was 7,5 months (range: 2-32). Overall incidence of recurrence was 80% (36/45) in patients treated with concomitant TMZ, and 90,9% (10/11) in pts treated only with postoperative RT. 44/46 recurrences (95,7%) were observed within the volume covered by the 95% isodose line, 2 recurrences were defined out of the field. MGMT methylation confirmed as a significant prognostic factor either for mean time to progression (9 vs. 8 months) than for recurrence rate (74% vs. 92%). In our series MGMT methylation was marginally related to the pattern of recurrence (central versus marginal + out of the field). Recurrence occurred inside the RT fields in 21/31 patients with MGMT methylated status (67,7%) and in 23/25 patients with MGMT unmethylated status (92%). We observed only two recurrences outside the radiation field, both in patients with MGMT methylated status. Conclusions: The analysis of our data shows that in GBM patients radically resected it is still adequate to limit postoperative RT to the surgical cavity + residual disease when present +>2 cms, including in the CTV areas of hyperintensity inthe T2 or FLAIR sequences of postoperative MRI. These data must however be interpreted with caution, since disease free methylated patients, who represent the great majority of progression free population, are still at risk of relapse. EP-1053 Efficacy and toxicity of chemo-radiotherapy in Hodgkinís lymphoma: A single institution experience A. Di Biase1, M. Conson1, L. Cella2, N. Puglese3, M. Picardi3, F. Doria1, R. Solla2, R. Liuzzi2, M. Salvatore1, R. Pacelli1 1 Università Federico II, Radioterapia, Napoli, Italy 2 Istituto di Biostrutture e Bioimmagini - C.N.R., Radioterapia, Napoli, Italy 3 Università Federico II, Ematologia, Napoli, Italy Purpose/Objective: Hodgkin’s lymphoma (HL) is a malignancy characterized by high sensitivity to chemo- (CH) and/or radiotherapy (RT) and high curability. At least 80% of patients with HL diagnosis will be today cured from the disease. Historically, however, the efficiency of the therapy and the consequent long life span expectation of the survivors, were badly affected by the iatrogenic late effects, particularly noteworthy considering the low mean age of the HL patient population. Feared long term side effects of the treatment included heart, lung diseases, and risk of radiation-induced second malignancies. In this retrospective study we analyse the data on HL patients treated in our institution in the last decade, showing the results about disease outcome and treatment related toxicity of a HL patients population homogeneously treated with modern schedule of chemotherapy and involved field three dimensional conformal RT (3DIFRT).

Purpose/Objective: In order to assess if the margins from GTV to CTV that we currently employ (surgical cavity + residual disease when present + >2cms, including in the CTV areas of hyperintensity in the T2 or FLAIR sequences of postoperative MRI) are adequate to cover the area of microscopic infiltration around the tumor, we evaluated for recurrence site patients (pts) treated with postoperative RT+/concomitant and maintenance TMZ from January 2009 to June 2012.

Materials and Methods: All patients received 4–6 cycles of ABVD-like chemotherapy. 3D-IFRT was administered using 6-20 MV photon beams with a total median dose of 32 Gy (range 20.8-41.4) in daily fractions of 1.5, 1.6 or 1.8 Gy. The patients were followed after the treatment by interview and physical examination every three months for the first year, every 6 months until the third year and yearly thereafter, while CT or PET/CT scan were programed every 6 months for the first 2 years and yearly thereafter. Electrocardiography and echocardiography before CH, after CH and before RT, and periodically after the end of RT. Echocardiography was used to estimate aortic, mitral, tricuspid and pulmonary valves regurgitation and stenosis. Thyroid stimulating hormone (TSH), free triiodo-thyronine (FT3), free thyroxine (FT4), and thyroglobulin antibody (TGA) blood levels were evaluated. All patients have been monitored for lung disease/injury as part of clinical routine during CHT, after CHT before RT, and after RT. CT scans were checked to detect radiation induced lung injury (RILI). Signs and symptoms of RILI were scored according to the RTOG late toxicity scoring system. The development of second neoplasms was also registered.

Materials and Methods: We limited our analysis to 56 completely resected pts (45 pts: RT+ TMZ, 11 pts: RT alone) in which methylation status of MGMTprecursor had been assessed to reduce the possible bias related to the generally rapid progression of the disease after

Results: One Hundred thirty two consecutive patients, 66 male and 66 female, median age 28 year (range 15 -70), affected by classical Hodgkin’s lymphoma, underwent radiation treatment between November 2001 and October 2012 at our Radiation Oncology department. One

EP-1052 Patterns of failure after postoperative radiation therapy and chemotherapy in completely resected glioblastoma D. Balestrini1, C. Degli Esposti1, A. Baldissera1, O. Martelli1, F. Salvi1, E. Donini1, G. Frezza1 1 Ospedale Bellaria Azienda USL di Bologna, Unità Operativa di Radioterapia, Bologna, Italy

S4 Hundred four (79%) patients were at stage I-II of disease and 28 (21%) at stage III-IV. At a median follow up time of 73 months (range 12-128) 128 out of 132 patients are alive with 124 free of relapse, for an overall survival (OS) of 97% and a disease free survival (DFS) of 94%. Asymptomatic heart valvular toxicity developed in 42% of patients, while all grade RILI and hypothyroidism in 16%, and 32% of patients. Two cases of solid, and two cases of hematologic malignancies were registered. Conclusions: Sequential treatment with chemotherapy and 3D-IFRT is effective and well tolerated for the treatment of Hodgkin’s lymphoma. Longer follow up is necessary to assess the toxicity profile of 3D-IFRT. EP-1054 Can hypofractionated stereotactic re-irradiation improves the outcome in patients with recurrent glioblastoma? M. Galeandro1, P. Ciammella1, A. Podgornii1, E. Cagni1, A. Botti1, C. Iotti1 1 Arcispedale S. Maria Nuova, Advanced Technologies, Reggio Emilia, Italy Purpose/Objective: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7-9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists.

ESTRO 33, 2014 surgical resection but had an early relapse and two other were treated without histological proof. Median number of TMZ cycles was 4 [3 - 7] and median number of BV cycles was 8 [5 - 12]. Tolerance was acceptable. Grade 3-4 toxicity was observed in 4 patients (28,6%). Eleven patients (78.5%) were able to receive a complete dose of radiotherapy (60 Gy ; 2Gy/day) after impact on tumor volume by the neoadjuvant treatment. Three patients (21.5%) had early clinical or radiological disease progression. After radiotherapy, 8 patients (57%) had stable disease and 3 (21%) a partial response according to RANO criteria (Fig 1). Neo-adjuvant treatment allowed for a reduction or cessation of corticosteroid treatment in 5 patients (36%) and to stabilize the steroid dose in 6 patients (43%). The median dose of methylprednisolone was 32 mg/day [8 - 100 mg] before treatment and 24 mg/day after treatment [0 - 64 mg]. An improvement of KPS was registered in 6/14 patients (42.9%) and no change of KPS in 7/14 patients (50%). Median PFS was 50 weeks [3 – 113 weeks]. The median OS was 58 weeks [16 – 136 weeks]. Six patients were still alive when data were analyzed. Conclusions: For the majority of the selected patients, a complete radiotherapy treatment with concomitant TMZ and BV was performed. It is likely that there was a beneficial effect of this neo-adjuvant treatment on OS and PFS. Although this data is from a retrospective analysis using small number of patients, this study might indicate that TMZ and BV association in neo-adjuvant is a crucial step in treatment for bulky GBM patients. These encouraging results should be confirmed by prospective study.

Materials and Methods: We analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions. Results: Of 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6–54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption. Conclusions: Our results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient. EP-1055 Neodjuvant Temozolomide and Bevacizumab for bulky glioblastoma before radiotherapy Darmon1, M. Boone2, B. Chauffert2, B. Gubler3, C. Desenclos4, H. Evestre5, A. Coutte1 1 University Hospital of Amiens, Radiotherapy, Amiens, France 2 University Hospital of Amiens, Medical Oncology, Amiens, France 3 University Hospital of Amiens, Laboratory of Oncobiology, Amiens, France 4 University Hospital of Amiens, Neurosurgery, Amiens, France 5 University Hospital of Amiens, Anatomopathology, Amiens, France Purpose/Objective: The treatment of patients with bulky or multifocal glioblastoma (GBM) newly diagnosed, in which any local treatment is contraindicated, is not well established. The main objective was to evaluate the possibility of reducing the tumor volume with a combination of Temozolomide (TMZ) and Bevacizumab (BV) in order to be able to perform a complete radiotherapy. Secondary objectives were to register toxicity, overall survival (OS), progression-free survival (PFS), clinical and radiological outcomes and corticoid consumption. Materials and Methods: This is a retrospective single center pilot study, carried out between December 2010 and July 2013 in patients with bulky or multifocal GBM for whom radiotherapy was initially contraindicated according to tumor volume to the first MRI. All patients received a treatment combining TMZ, 150 to 200 mg/m 2/day for 5 days every 28 days, and BV, 10mg/m2 every 14 days. Response to treatment and the possibility to perform radiotherapy were evaluated by clinical examination and MRI. Results: Fourteen patients were analyzed (median age 59 years, median KPS 70). Ten patients (71%) were classified in the RTOG RPA groups V-VI and 4 patients in the RPA group IV. Two patients first underwent a

EP-1056 Radiosurgery and stereotactic radiotherapy for brain metastases: an early single-institution experience V. Borzillo1, F.M. Giugliano1, R. Di Franco2, S. Falivene2, L. Iadanza3, M. Mormile3, V. Ravo1, P. Muto1 1 Istituto Nazionale Tumori Fondazione Pascale, Radiotherapy, Napoli, Italy 2 Seconda Università degli Studi di Napoli, Radiotherapy, Napoli, Italy 3 Istituto Nazionale Tumori Fondazione Pascale, Physics, Napoli, Italy Purpose/Objective: Brain metastases (BMs)are the most common intracranial malignant neoplasm in adults and occur in approximately 20– 40% of all cancer patients. Many different therapeutic options are available: whole-brain radiotherapy (WBRT), surgery, radiosurgery (RS) and stereotactic radiotherapy(SRT). We report our early experience in the treatment of patients with a single or multiple(2-4) BMs using Cyberknife® (CK) radiosurgery system (Accuray Inc., Sunnyvale, CA, USA). Materials and Methods: From November 2012 to November 2013, we treated 68 patients with BMs (for a total of 111lesions) using the CK, an image-guided frameless robotic RS/SRT system. Patients,33 M and 35 F, had median age of 59 aa (29-86), Karnofsky performance status >70 in 97%. They classified as class II in 90% of cases RPA (RecursivePartitioning Analysis). The GPA score was 1.5-2.0 in 43% of