M. Ferro

A PHASE I DOSE-ESCALATION STUDY (ISIDE-BT-1) OF ACCELERATED IMRT WITH TEMOZOLOMIDE IN PATIENTS WITH GLIOBLASTOMA

PURPOSE To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. METHODS AND MATERIALS A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed +/- enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade >or=3 or any hematological toxicity rated as >or=4 by Radiation Therapy Oncology Group (RTOG) criteria. RESULTS Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. CONCLUSION Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

Short-Course Radiotherapy in Elderly Patients with Early Stage Non-Melanoma Skin Cancer: A Phase II Study

Aim: To evaluate outcome of an accelerated radiotherapy (RT) regimen in elderly patients with an early stage non-melanoma skin cancer (NMSC). Methods: Total RT dose was 30 Gy in 5 Gy fractions in six consecutive days. Results: Thirty-one patients were enrolled. Fourteen were aged ≥80 years. Acute skin and observed late toxicity were exclusively of grade 1. Thirty patients showed a complete response (median follow-up 30 months). Two-year actuarial local control was 93.2%. The cosmetic result was mostly judged as good or excellent. Conclusions: Short-course RT in elderly NMSC patients produces >90% local control of disease.

A phase I study of short-course accelerated whole brain radiation therapy for multiple brain metastases

PURPOSE To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. METHODS AND MATERIALS A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class>or=2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status≤3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity≥grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. RESULTS Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). CONCLUSIONS Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

Results of a phase II study of Short-course Accelerated Radiation Therapy (SHARON) for multiple brain metastases.

Objectives:To assess the effectiveness of a SHort-course Accelerated RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Materials and Methods:A phase II clinical trial was designed. Eligibility criteria included patients with at least 3 brain metastases or metastatic disease in >3 organ systems, and Eastern Cooperative Oncology Group performance status of ⩽3. Fifty patients were treated with whole brain radiotherapy at 18 Gy (4.5 Gy per fraction) in 2 days with a twice daily fractionation. The primary endpoint was the assessment of efficacy in terms of overall survival. Results:Characteristics of the 50 enrolled patients were: male/female: 24/26; median age: 65 years (range, 45 to 80 y). Eastern Cooperative Oncology Group performance status was <3 in 42 patients (84%). Nineteen patients (38%) were considered to have recursive partitioning analysis class 3 disease. Grade 1-2 acute neurological (46%) and skin (24%) toxicities were recorded. Three patients (6%) experienced neurological grade 3 acute toxicity. With a median follow-up time of 6 months (range, 1 to 18 mo) 2 skin grade 1 late toxicities has been observed. Seventeen of 27 symptomatic patients showed an improvement or resolution of baseline symptoms (overall palliative response rate: 63.0%; 95% confidence interval, 36.6%-82.4%).Two-month overall survival was 86% (median survival time=7 mo). Conclusions:Short-course accelerated whole brain radiotherapy of 18 Gy in twice daily fractions for 2 consecutive days is tolerated and effective in terms of symptom relief and median survival time. These results justify a phase III comparison against the standard-of-care in this patient population (30 Gy in 10 fractions).

EP-1556: VMAT in nasopharyngeal tumor: clinical implications after a change in the dose calculation algorithm

Material and Methods: Firstly, a historical review of commissioning tests results on 3 different Varian linacs (Clinac iX, Unique, TrueBeam) was collected, for both old (2008: vs1) and new (2015: vs2) Varian test versions; original tests were extended to 10MV, 6FFF and 10FFF beams for TrueBeam. Data were collected monthly through portal vision (PV) images , for respectively 81, 21, and 42 entries for vs1. At the same, delivery parameters were extracted from actual patients plans (3911plans, 6833arcs) and stratified according to the types of treatment. From our experience, we felt the needs to have a more flexible instrument tuned on our clinical practice, able to support us in a possible troubleshooting. A family of new T2 and T3 plans was generated. In addition to the traditional analysis of the images, a direct comparison with the open reference field is proposed to define a more reliable baseline for the monitoring of each strip trend.

Policies for reirradiation of recurrent high-grade gliomas: a survey among Italian radiation oncologists

Purpose: To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach. Methods: In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach. Results: A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter <5 cm and an interval from primary radiation ≥6 months, were the prevalent predictive factors considered for reRT. Sixty percent of reirradiated patients had already received a salvage therapy, either chemotherapy (40%) or reoperation (20%). The most common approach for reRT was fractionated stereotactic radiotherapy to a mean (photon) dose of 41.6 Gy. Conclusions: Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

PO-0790: Radiation-induced mesothelioma among solid cancer survivors: an analysis of the seer cohort

Sant’Orsola-Malpighi HospitalUniversity of Bologna, Radiation Oncology CenterDepartment of ExperimentalDiagnostic and Specialty Medicine DIMES, Bologna, Italy Sant’Orsola-Malpighi HospitalUniversity of Bologna, Department of Medical Physics, Bologna, Italy Fondazione di Ricerca e Cura “Giovanni Paolo II”Catholic University of Sacred Heart, Radiotherapy Unit, Campobasso, Italy Ospedale Bellaria, Radiotherapy Department, Bologna, Italy

PO-0774: Extra-cranial radiosurgery in oligometastatic disease: a dose escalation study (Destroy-2)

Results: SBRT treatment: maximum small bowel and duodenum dose-volume constraints were exceeded in 5/30 (16.7%) and 2/30 (6.7%), respectively. Dose to OARs was: small bowel: Dmax 31.5-40.5 Gy, V30 0.2-13.4 cc; duodenum: Dmax 35.7-36.6 Gy, V30 2.1-3.7 cc. SBRS treatment: maximum small bowel and duodenum dosevolume constraints were exceeded in 2/21 patients (9.5%) and 1/21 patient (4.7%), respectively. Dose to OARs was: small bowel: Dmax 15.6-16.3 Gy, V12 1.7-8.5 cc; duodenum Dmax 16.0 Gy, V12 0.1 cc. With a median follow up of 24 months after SBRT and 18 months after SBRS, no early or late severe toxicity was observed in patients in whom constraints were not respected.

EP-1633: Optimal dose prescription in Linac-based SBRT using VMAT: a “Pareto fronts” approach

Material and Methods: Three spherical-shaped targets of different dimensions (20cc, 55cc and 101cc) were selected from our clinical database. GTV included macroscopic disease defined on CT. PTV was defined based on internal margin and setup margin. Healthy liver was considered whole liver minus GTV. A single fraction dose of 26 Gy was prescribed (PD=Prescription Dose). VMAT plans were generated with Ergo++ (Elekta) using a 10MV single arc. Pareto fronts based on (i) different MLC block margin around PTV (ranging from +4mm to -2mm with 1 mm step) and (ii) different prescription isodose line (IDS) ranging from 50% to 100% of PD were produced. For each block margin, the greatest IDS fulfilling the two criteria: 95% of PTV volume reached 100% of PD and 90% of PTV reached 99% of PD was considered as that providing the optimal clinical plan for target coverage. The liver mean dose, V7Gy and V12Gy were used together with the PTV coverage (1-V100) to generate the fronts. The ratio of the prescription isodose surface volume to PTV volume (conformity index CI), gradient index (GI=V50/V100), the ratio of normal tissue volume receiving 50% of prescription dose and PTV volume (NTV50/PTV), homogeneity index (HI=D2%/PD) and healthy liver irradiation in terms of mean dose, V7Gy and V12Gy were calculated to compare different plans

EP-2117: Is Rotational shifts necessary in SBRT? A geometric analysis using a 6-degree of freedom(6-DoF)couch

Material and Methods: The study has been performed on 10 breast cancer patients positioned on All In One system, and 10 patients treated using dedicated breast board. Selected patients represent average breast cancer patients. Patients with special setup needed, were excluded. (eg. patients with reduced arm mobility, patients with large contra lateral breast etc.). On both fixation systems the same setup protocol was used. Imaging and setup correction were performed on fractions 1, 2, 3, 8, 13, and every 5th further fraction. All the correction data were written in specially prepared forms. All the data collected were entered in excel worksheet, and further analyzed.