INT-SCART-001: A Phase I Study Evaluating the Safety of Stereotactic Central Ablative Radiation Therapy (SCART) for Bulky Metastatic or Recurrent Cancer.

Despite advances in screening and surveillance, patients continue to present with both bulky primary and metastatic tumors. Some patients presented with recurrent bulky cancer in prior treated radiation fields. Spatially Fractionated Radiation therapy (SFRT) has a history of over 100 years. The principle of SFRT is distinctive from the standard radiation approaches, as it treats the total tumor with a non-uniform dose, effectively treating the tumor while staying within normal tissue tolerance of the surrounding structures. Historically, SFRT is frequently used to treat bulky malignant tumors with a high radiation dose in the stereotactic radiosurgery (SRS)/stereotactic body radiotherapy (SBRT) dose range (10-20 Gy per fraction) using megavoltage x-ray beams. The application of SFRT, historically known as GRID therapy, has produced dramatic relief of severe symptoms, significant objective regression, above average local control rates and minimal toxicity in palliative settings.

High-dose GRID radiotherapy, sometimes termed spatially-fractionated GRID radiotherapy (SFGRT), is a treatment modality that was introduced in 1909 and commonly used through the 1930's . In 1909, Kohler in Germany described radiation delivered through a perforated screen with regularly spaced blocked areas that created an effect similar to treatment with multiple small pencil beams. This spatially fractionated radiation, in contradistinction to current approaches, does not attempt to treat the total tumor volume with a uniform dose. Instead, this technique allows the delivery of high doses of radiation in clusters of small areas without producing prohibitive normal tissue damage to skin and subcutaneous tissues. In its early applications, two-dimensional grid fields were used, typically with orthovoltage beams. The grids were usually composed of open/shield circular or square shapes ranging in size from 0.5 to 1.5 cm. The application was mainly for the treatment of advanced bulky tumors.

However, the technique of GRID radiotherapy has not evolved significantly since its inception in the early 1900's, and is not the optimal method of delivering spatially fractionated radiation in the modern era. GRID has the limitation of delivering relatively high doses of radiation to normal tissues, depending on tumor location, as it is delivered via a single beam that must pass through normal tissues to reach its target. Most importantly, the highest-dose regions of the grid are superficial, and often are outside of the tumor target itself.

The basic principle of the LATTICE Radiotherapy (LRT) is to create within tumor volume multiple localized high-dose islands (12 Gy and higher) with a certain degree of separation to form low dose regions (3 Gy or lower). In an extreme case, one or two focused dose islands could be introduced in a small tumor.

Modern radiotherapy methods are readily available to deliver 3D high-dose LATTICE radiotherapy with superior dosimetry compared to the 2D GRID technique . An array of focused high-dose volumes, in essence a lattice of doses in 3D, can be generated through modern techniques resulting in highly heterogeneous dose distributions within the tumor volume, leaving adjacent and peripheral normal tissue minimally exposed.