Anchored Transponder Guided Lung Radiation Therapy.

PURPOSE: The Calypso Beacon transponder has been modified by the addition of a nitinol anchor feature to allow for positional stability when implanted bronchoscopically into the lung. The purpose of this study was to confirm the feasibility and safety of anchored transponder placement and feasibility of lung target localization and tracking. METHODS AND MATERIALS: This study enrolled patients with histologically confirmed cancer in the lung (primary or metastatic) who were scheduled to receive external beam radiation therapy. Three anchored transponders were implanted via flexible bronchoscopy into small (approximately 2- to 2.5-mm diameter) airways. Patient alignment at each radiation fraction was performed with the Calypso system, and anchored transponder position was tracked during radiation delivery. The primary endpoint was defined as the ability to localize at least 85% of the patients during the first week of treatment. Four follow-up visits were specified including a posttreatment assessment and every 3 months up to 1 year. RESULTS: A total of 69 patients underwent anchored transponder placement, and all 207 implanted anchored transponders were visible on the treatment-planning simulation computed tomography scan. Sixty-seven patients underwent radiation therapy, and localization was successful in 66 cases (98.5%). With 1 failure in 67 cases, the P value for rejecting the null hypothesis was <.001 and the primary objective of the study met. Five adverse events in 5 patients were potentially attributed to the study device or implantation procedure, consisting of pneumonia (2 cases), pleural abscess (1 case), and pneumothorax (2 cases). Two serious events (cardiac arrest and acute hypotension) were attributed to anesthesia during the implantation procedure. CONCLUSIONS: This study strongly supports that anchored transponders are safe, positionally stable, and useful for lung tumor localization and monitoring.

Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer.

BACKGROUND: The efficiencies of T cell based immunotherapies are affected by insufficient migration and activation of tumor specific effector T cells in the tumor. Accumulating evidence exists on the ability of ionizing radiation to modify the tumor microenvironment and generate inflammation. The aim of this phase I/II clinical trial is to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with pancreatic cancer. METHODS/DESIGN: This trial has been designed as an investigator initiated; prospective randomised, 4-armed, controlled Phase I/II trial. Patients who are candidates for resection of pancreatic cancer will be randomized into 4 arms. A total of 40 patients will be enrolled. The patients receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation precisely targeted to their pancreatic carcinoma. Radiation will be delivered by external beam radiotherapy using a 6 MV Linac with IMRT technique 48 h prior to the surgical resection. The primary objective is the determination of an active local external beam radiation dose, leading to tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include local tumor control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality, as well as quality of life. Further, frequencies of tumor reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. An interim analysis will be performed after the enrollment of 20 patients for safety reasons. The evaluation of the primary endpoint will start four weeks after the last patient's enrollment. DISCUSSION: This trial will answer the question whether a low dose radiotherapy localized to the pancreatic tumor only can increase the number of tumor infiltrating T cells and thus potentially enhance the antitumor immune response. The study will also investigate the prognostic and predictive value of radiation-induced T cell activity along with transcriptomic and proteomic data with respect to clinical outcome.