E. Villa

Stereotactic body radiation therapy: A promising chance for oligometastatic breast cancer

BACKGROUND Multidisciplinary management of oligometastatic breast cancer with local therapy could improve disease control. The aim of our study is the assessment of safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) in selected subset of patients. PATIENTS AND METHODS Oligometastastic patients from breast cancer were treated with SBRT for 1-3 lung and liver lesions, in an observational study. Inclusion criteria were: age >18 years, ECOG 0-2, diagnosis of breast cancer, no extrapulmonary and/or extrahepatic disease, other metastatic sites stable or responding after chemotherapy were allowed, no life threatening conditions, less than 5 lung and liver lesions (with maximum diameter <5 cm), chemotherapy completed at least 3 weeks before treatment, written informed consent. Prescription dose ranged between 48 and 75 Gy in 3 or 4 consecutive fractions. Primary end-point was local control (LC). Secondary end-points were toxicity, overall survival (OS) and progression-free survival (PFS). RESULTS From April 2010 to June 2014, 33 patients for a total number of 43 lesions were irradiated. Median follow up was 24 months (range 3-59). Actuarial LC rates were 98% at 1 year and 90% at 2 and 3 years. Complete response, partial response and progressive disease were detected in 25 (53.2%), 16 (34%), and 6 (12.8%) lesions, respectively. Median OS was 48 months. Actuarial OS rates at 1 and 2 years were 93% and 66% respectively. Median PFS was 11 months, with a PFS rate at 1 and 2 years of 48% and 27%, respectively. At univariate analysis DFI >12 months, hormonal receptor positivity, medical therapies after SBRT showed a significant impact on OS. Treatment was well tolerated, with no G3-4 toxicities. CONCLUSIONS SBRT is a safe and feasible alternative treatment of liver and lung oligometastases from breast cancer, in selected patients not amenable to surgery, with good local control and survival rate.

The role of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in the elderly

OBJECTIVE To report about clinical outcome of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in elderly patients. METHODS Patients with 1-4 inoperable metastases were treated with SBRT. Dose prescription ranged from 40 to 75 Gy in 3-8 fractions. SBRT was delivered using the volumetric modulated arc therapy technique with flattening filter-free photon beams. The primary end points were in-field local control (LC) and toxicity. Secondary end points were overall survival (OS) and disease-specific survival (DSS). RESULTS 82 patients with 111 total metastases were treated. Median age was 79 years. 64 patients (78%) had a single lesion; the remaining patients had 2-4 lesions. 16 (14.4%) lesions were localized in the abdomen, 50 (45.0%) in the liver and 45 (40.5%) in the lungs. Local response was observed for 87 lesions (78.4%) while local progression was observed in 24 lesions (21.6%). Actuarial 1-year LC was 86.8% ± 3.3%. Actuarial 1-year OS was 93.6% ± 2.7%. 2-year findings were 76.3% ± 4.4% and 72.0% ± 5.6%, respectively. Actuarial 1- and 2-year DSS results were 97.5% ± 2.0% and 81.6% ± 4.9%, respectively. Treatment-related Grade 2-3 toxicity was observed in five patients (4.2%); Grade 1 toxicity in seven patients (5.9%) and no toxicity was observed in 85.4% of the cases. CONCLUSION SBRT is a safe and effective therapeutic option for the treatment of oligometastatic disease in the elderly with acceptable rates of LC and low treatment-related toxicity. ADVANCES IN KNOWLEDGE The use of SBRT for oligometastatic disease in the elderly can be considered as a valuable approach, particularly for patients with fragile status or refusing other approaches.

Hypofractionated Stereotactic Radiation Therapy in Recurrent High-Grade Glioma: A New Challenge

Purpose The aim of this study was to evaluate outcomes of hypofractionated stereotactic radiation therapy (HSRT) in patients re-treated for recurrent high-grade glioma. Materials and Methods From January 2006 to September 2013, 25 patients were treated. Six patients underwent radiation therapy alone, while 19 underwent combined treatment with surgery and/or chemotherapy. Only patients with Karnofsky Performance Status (KPS) > 70 and time from previous radiotherapy greater than 6 months were re-irradiated. The mean recurrent tumor volume was 35 cm3 (range, 2.46 to 116.7 cm3), and most of the patients (84%) were treated with a total dose of 25 Gy in five fractions (range, 20 to 50 Gy in 5-10 fractions). Results The median follow-up was 18 months (range, 4 to 36 months). The progression-free survival (PFS) at 1 and 2 years was 72% and 34% and the overall survival (OS) 76% and 50%, respectively. No severe toxicity was recorded. In univariate and multivariate analysis extent of resection at diagnosis significantly influenced PFS and OS (p < 0.01). Patients with smaller recurren tumor volume treated had better local control and survival. Indeed, the 2-year PFS was 40% (≤ 50 cm3) versus 11% (p=0.1) and the 2-year OS 56% versus 33% (> 50 cm3), respectively (p=0.26). Conclusion In our experience, HSRT could be a safe and feasible therapeutic option for recurrent high grade glioma even in patients with larger tumors. We believe that a multidisciplinary evaluation is mandatory to assure the best treatment for selected patients. Local treatment should also be considered as part of an integrated approach.

What is the role of [11C]choline PET/CT in decision making strategy before post-operative salvage radiation therapy in prostate cancer patients?

To the Editor,The use of [11C]choline positron emission tomography (PET) seems to be promising with a prostate-specific antigen (PSA) rise after primary treatment in prostate and appears superior t...

11C Choline PET Guided Salvage Radiotherapy with Volumetric Modulation Arc Therapy and Hypofractionation for Recurrent Prostate Cancer after HIFU Failure: Preliminary Results of Tolerability and Acute Toxicity

The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients undergoing salvage radiotherapy after high-intensity focused ultrasound (HIFU) failure. From 2005 to 2011 a total of 15 patients were treated with HIFU as primary radical treatment. Between July 2011 and February 2013, all 15 patients presented biochemical relapse after HIFU and 11C choline PET documenting intrapostatic-only failure. Salvage EBRT was performed with moderate hypofractionation schedule in 28 fractions with volumetric modulation arc therapy (VMAT). Genito-urinary (GU) and rectal and bowel toxicity were scored by common terminology criteria for adverse events version 4 (CTCAE V.4) scale. Biochemical response was assessed by ASTRO Phoenix criteria. Median age of patients was 67 years (range: 53–85). The median Gleason score was 7 (range: 6–9). The median prostate specific antigen (PSA) at the time of biochemical relapse after HIFU was 5.2 ng/mL (range: 2–64.2). Seven of the 15 patients received androgen deprivation therapy (ADT) started after HIFU failure, interrupted before 11C choline PET and radiotherapy. Median prescribed dose was 71.4 Gy (range: 71.4–74.2 Gy) in 28 fractions. No radiation related major upper gastrointestinal (GI), rectal and GU toxicity were experienced. GU, acute grade 1 and grade 2 toxicities were recorded in 7/15 and 4/15 respectively; bowel acute grade 1 and grade 2 toxicities in 4/15 and 1/15; rectal acute grade 1 and grade 2 toxicities in 3/15 and 2/15 respectively. No grade 3 or greater acute or late toxicities occurred. Biochemical control was assessed in 12/15 (80%) patients. With a median follow up of 12 months, three out of 15 patients, with biochemical relapse, showed lymph-nodal recurrence. Our early clinical results and biochemical data confirm the feasibility and show a good tolerance of the 11C choline PET guided salvage radiation therapy after HIFU failure. The findings of low acute toxicity is encouraging, but longer follow-up is needed to assess late toxicity and definitive outcomes.

Follow-up of elderly patients with urogenital cancers: Evaluation of geriatric care needs and related actions

OBJECTIVES To investigate a comprehensive geriatric assessment (CGA) with subsequent investigation of healthcare patterns in older patients with urological cancers undergoing initial surgery or radiotherapy, to verify the usefulness of the incorporation of geriatric principles in future care plans. MATERIAL AND METHODS This is a prospective cohort study. From November 2011 to March 2015, CGA was offered to all patients aged 70+ years treated with radiotherapy or surgery at seven tertiary centers. Patients were classified as fit, vulnerable, or frail according to Balduccis definition. CGA and follow-up data were collected by two trained evaluators at 6 and 12months. The information collected was not available to the caring physicians during follow-up. RESULTS CGA was performed in 453 patients with prostate cancer (295), bladder cancer (126), or kidney cancer (32). 40% of patients with prostate cancer were fit, 47% vulnerable, and 13% frail. The corresponding values for renal cancer were 25%, 40%, and 34%, and for bladder cancer, 21%, 42%, and 37%. During follow-up, 60% of patients with cardiac diseases, 42% of those with diabetes/other metabolic disorders, 35% of those with hypertension, and 35% of those with respiratory diseases were followed by a specialist (for these severe/extremely severe comorbidities). Of 16 patients with ADL impairment and 63 with IADL impairment, only 4 (25%) and 6 (10%), respectively, were referred to a rehabilitation service. Only one case was referred to a geriatrician. CONCLUSIONS Appropriate clinical care patterns are advisable to improve quality of survivorship in older patients with urological cancers.

Urinary bladder preservation for muscle-invasive bladder cancer: a survey among radiation oncologists of Lombardy, Italy

Aims and Background Bladder preservation is a treatment option in muscle-invasive bladder carcinoma. The most investigated approach is a trimodality schedule including maximum transurethral resection of bladder tumor (TURBT) followed by chemoradiotherapy. Our aim was to evaluate the use of bladder preservation by radiation oncologists of the Lombardy region in Italy. Methods and Study Design A survey with 13 items regarding data of 2012 was sent to all 32 radiotherapy centers within the collaboration between the Lombardy Oncological Network and the Lombardy Section of the Italian Society of Oncological Radiotherapy. Results Thirteen centers (41%) answered the survey; the presented data come from 11 active centers. In these centers, 11,748 patients were treated with external-beam radiotherapy in 2012, 100 of whom having bladder cancer (0.9%). 74/100 patients received radiotherapy as palliative treatment for T, N or M lesions. A further 9 and 5 patients received radiotherapy for oligometastatic disease (ablative doses to small volumes) and postoperatively, respectively. Bladder preservation was performed in 12 cases and included trimodality and other strategies (mainly TURBT followed by radiotherapy). A multidisciplinary urology tumor board met regularly in 5 of 11 centers. All responders declared their interest in the Lombardy multicenter collaboration on bladder preservation. Conclusions Our survey showed that bladder preservation is rarely used in Lombardy despite the availability of the latest radiotherapy technologies and the presence of an urology tumor board in half of the centers. The initiative of multicenter and multidisciplinary collaboration was undertaken to prepare the platform for bladder preservation as a treatment option in selected patients.

PO-0705: Clinical outcomes for inoperable HCC treated with SBRT: results on 71 patients and 102 lesions

Material and Methods: 395 patients with stage III thoracic ESCC treated with radical esophagectomy from Jan, 2008 to Dec, 2011 were enrolled in this study. No patients has accepted preoperative adjuvant therapy. There were 302 males and 93 females; median ages was 60 years old (range 33-83). There were 33 patients located in upper-, 273 in middleand 89 in low-segment. 375 patents has operated with two-field and 22 with three-field esophagectomy. The median number of dissected lymph nodes were 10 per case (range 1-34). There were 244 with stage IIIA, 106 with IIIB and 45 with IIIC. There were 97 patients received with surgery alone, 212 with postoperative chemotherapy(POCT), 86 with PORT(30 with POCT and PORT). Diagnosis of recurrence was parimarily based on CT images, some of which were biopsy-confirmed. The location and time of tumor recurrences were analyzed.

PO-0710: Clinical outcomes for inoperable HCC treated with SBRT: mono- institutional experience

Purpose/Objective: Objective: Patients with locally recurrent rectal cancer have severe morbidity and poor quality of life. Most are ineligible for surgery, and combined re-irradiation and chemotherapy provides limited symptom palliation and tumor control [1]. Clinical data suggests that adding hyperthermia to radiation improves tumor response [2]. However, past studies used invasive temperature sensors that were poorly tolerated and provided insufficient thermal dosimetry. The objective of this study was to evaluate the feasibility in pigs of using MRI-HIFU to achieve mild hyperthermia in normal tissue targets that match typical locations for recurrent rectal cancer; and the quality of MR thermometry in consenting volunteers with biopsy-proven primary rectal cancer. Materials and Methods: Preclinical validation: The feasibility of MR-HIFU hyperthermia was evaluated in a swine model (N=6, study approved by the Local Animal Care Committee). Imaging and hyperthermia were performed using a clinical MRI (Achieva 3T, Philips Healthcare) with an integrated MR-HIFU system (Sonalleve, Philips Medical Systems). Different targets at thigh muscle (at the rectal wall and deep locations) were evaluated. Thermal maps were acquired in 6 slices along the beam were obtained every 3.2s. Sonications were prescribed with 18 mm diameter treatment regions at 1MHz with target temperature of 42-42.5°C, for 10-60 min. Human imaging study The quality of MR thermometry of rectal cancers using MRHIFU was evaluated with an imaging-only study (no heating) including 6 consenting volunteers with rectal cancer. This study was approved by the Sunnybrook Research Ethics Board. Anatomical and MR thermometry images were acquired using the same MRI and MR-HIFU system and parameters as in the preclinical study. In 3/6 subjects, rectal filling with 200-300 mL of saline was used to reduce motionrelated artefacts in MR thermometry. Thermometry was performed in imaging slices located at the tumor. Results: Mean target temperature in the animal study matched the desired hyperthermia temperature to within 0.2°C, varying temporally with a standard deviation of 0.5°C or lower. No evidence of tissue changes were observed on contrast-enhanced imaging or at necropsy. The imaging study with patients showed that MR-based temperature remained stable especially when rectal filling was used to reduce bowel motion. Figure 1.