C. Franzese

Radiotherapy and immunotherapy: Can this combination change the prognosis of patients with melanoma brain metastases?

Brain metastases are a common occurrence in patients with melanoma. Prognosis is poor. Radiotherapy is the main local treatment for brain metastases. Recently, immunotherapy (i.e. immune checkpoints inhibitors) showed a significant impact on the prognosis of patients with metastatic melanoma, also in the setting of patients with brain metastases. Despite various possible treatments, survival of patients with melanoma brain metastases is still unsatisfactory; new treatment modalities or combination of therapies need to be explored. Being immunotherapy and radiotherapy alone both efficient in the treatment of melanoma brain metastases, the combination of these two therapies seems logical. Moreover radiotherapy can improve the efficacy of immunotherapy and the immune system plays a relevant role in the action of radiotherapy. Preclinical data support this combination. Clinical data are more contradictory. In this review, we will discuss available therapies for melanoma brain metastases, focusing on the preclinical and clinical available data supporting the possible synergism between radiotherapy and immunotherapy.

Can Stereotactic Body Radiation Therapy Be a Viable and Efficient Therapeutic Option for Unresectable Locally Advanced Pancreatic Adenocarcinoma? Results of a Phase 2 Study

Purpose: To assess the efficacy of stereotactic body radiotherapy in patients with unresectable locally advanced pancreatic cancer. Materials and Methods: All patients received a prescription dose of 45 Gy in 6 fractions. Primary end point was freedom from local progression. Secondary end points were overall survival, progression-free survival, and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. Results: Forty-five patients were enrolled in a phase 2 trial. Median follow-up was 13.5 months. Freedom from local progression was 90% at 2 years. On univariate (P < .03) and multivariate analyses (P < .001), lesion size was statistically significant for freedom from local progression. Median progression-free survival and overall survival were 8 and 13 months, respectively. On multivariate analysis, tumor size (P < .001) and freedom from local progression (P < .002) were significantly correlated with overall survival. Thirty-two (71%) patients with locally advanced pancreatic cancer received chemotherapy before stereotactic body radiotherapy. Median overall survival from diagnosis was 19 months. Multivariate analysis showed that freedom from local progression (P < .035), tumor diameter (P < .002), and computed tomography before stereotactic body radiotherapy (P < .001) were significantly correlated with overall survival from diagnosis. Conclusion: Stereotactic body radiotherapy is a safe and effective treatment for patients with locally advanced pancreatic cancer with no G3 toxicity or greater and could be a promising therapeutic option in multimodality treatment regimen.

Imaging biomarkers in primary brain tumours

We are getting used to referring to instrumentally detectable biological features in medical language as “imaging biomarkers”. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context.

11C-Choline-Pet Guided Stereotactic Body Radiation Therapy for Lymph Node Metastases in Oligometastatic Prostate Cancer

ABSTRACT Introduction: aim is outcome of 11C-Choline-PET guided SBRT on lymph node metastases. Materials and methods: patients with 1 – 4 lymph node metastases detected by 11C-choline-PET were treated with SBRT. Toxicity, treated metastases control and Progression Free Survival were computed. Results: twenty-six patients, 38 lymph node metastases were irradiated. No grade ≥ 2 toxicity. Median PSA-nadir after RT was 1.02 ng/mL. Post-treatment 11C-Choline-PET showed metabolic complete response in 17 metastases (44,7%), partial response in 9 metastases (38%). Conclusion: SBRT is effective and safe for lymph node metastases. PET is important in identification of gross tumor and evaluation of the response.

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.