Cyberknife

Sixteen consecutive patients with malignant melanoma were treated with ipilimumab and at least one instance of cranial radiation between 2008 and 2013 at our institution. This study was approved by our institutional review board as described in the Ackowledgments. No patient consent was required as this was a retrospective study.
Ipilimumab was generally given every three weeks for a total of four doses at a dose of either 3 mg/kg (n = 14) or 10 mg/kg (n = 2); patients achieving clinical benefit were offered maintenance therapy every twelve weeks. Cranial radiation was either WBRT or SRS. No patients received SRS as a planned boost. SRS was delivered using the Cyberknife (Accuray, Sunnvale, CA) system prescribed to the clinical tumor volume (CTV) which was equivalent to the planning tumor volume.

This study evaluated the effectiveness and toxicity of an EBRT combination of 46 Gray (Gy) with normal fractionation followed by a hypofractionated stereotactic boost (3 fractions of 6 Gy). The first part of the treatment was delivered using 3D conformal radiotherapy (3DCRT) or intensity modulated radiation therapy (IMRT) associated with image-guided radiotherapy (cone beam or megavoltage computed tomography). Next, stereotactic body radiotherapy (SBRT) was delivered using Cyberknife (Accuray, Inc., Sunnyvale, CA). Treatment volume included prostate and the first part of seminal vesicles and prostate only for EBRT and SBRT respectively. Prostate volume was delineated using planning MRI registration based on intraprostatic fiducials. None of these patients had received hormonal therapy before or during radiotherapy.

The tumors were irradiated with the Cyberknife (Accuray Incorporated, Sunnyvale, CA, USA). To accurately guide the radiation, the gastroenterologist placed three radio-opaque markers in or near the tumor (within 3cm of the tumor). Patients received a total of 40 Gray (Gy) of SBRT in five fractions on consecutive days. Radiation started at week 2, just after patients received the second vaccination of IMM-101. Immodulon Therapeutics Ltd. (Uxbridge, UK) produced and shipped pre-labeled IMM-101 vials to the pharmacy of the Erasmus MC University Medical Center. IMM-101 was injected intradermally over the deltoid muscle by the standard Mantoux intradermal injection technique. One mL was injected, which contained one milligram of IMM-101. IMM-101 was administered six times: i.e., on week 0, week 2, week 4, week 8, week 10 and week 12. Figure 1 illustrates the treatment schedule. At week 0, week 2, week 4, week 8 and week 14 blood draws were performed for immune-monitoring;, i.e., before planned study drug administration or SBRT treatment. One red 10 mL clot activator tube from BD Vacutainer^®, one 3 mL Tempus^TM RNA stabilisator tube and two 10 mL EDTA tubes from BD Vacutainer^® were collected. The blood was processed within six hours after collection. Plasma, serum and peripheral blood mono-nuclear cells (PBMCs) were isolated and cryopreserved.