Purpose: A dual modality SPECT-CT prototype system dedicated to uncompressed breast imaging (mammotomography) has been developed. The computed tomography subsystem incorporates an ultrathick K-edge filtration technique producing a quasi-monochromatic x-ray cone beam that optimizes the dose efficiency of the system for lesion imaging in an uncompressed breast. Here, the absorbed dose in various geometric phantoms and in an uncompressed and pendant cadaveric breast using a normal tomographic cone beam imaging protocol is characterized using both thermoluminescent dosimeter (TLD) measurements and ionization chamber-calibrated radiochromic film. Methods: Initially, two geometric phantoms and an anthropomorphic breast phantom are filled in turn with oil and water to simulate the dose to objects that mimic various breast shapes having effective density bounds of 100% fatty and glandular breast compositions, respectively. Ultimately, an excised human cadaver breast is tomographically scanned using the normal tomographic imaging protocol, and the dose to the breast tissue is evaluated and compared to the earlier phantom-based measurements. Results: Measured trends in dose distribution across all breast geometric and anthropomorphic phantom volumes indicate lower doses in the medial breast and more proximal to the chest wall, with consequently higher doses near the lateral peripheries and nipple regions. Measured doses to the oil-filled phantoms are consistently lower across all volume shapes due to the reduced mass energy-absorption coefficient of oil relative to water. The mean measured dose to the breast cadaver, composed of adipose and glandular tissues, was measured to be 4.2 mGy compared to a mean whole-breast dose of 3.8 and 4.5 mGy for the oil-and water-filled anthropomorphic breast phantoms, respectively. Conclusions: Assuming rotational symmetry due to the tomographic acquisition exposures, these results characterize the 3D dose distributions in an uncompressed human breast tissue volume for this dedicated breast imaging device and illustrate advantages of using the novel ultrathick K-edge filtered beam to minimize the dose to the breast during fully-3D imaging.

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PURPOSE: Severe and long-lasting lymphopenia occurs in 40% of patients with malignant gliomas and is associated with inferior survival. Inadvertent irradiation of circulating lymphocytes is a major contributor to this lymphopenia. Fingolimod causes striking but reversible lymphopenia by sequestering circulating lymphocytes in lymphoid tissues. Fingolimod could potentially reduce iatrogenic immunosuppression by decreasing the number of lymphocytes in circulation during radiation. However, combining radiation with fingolimod should result in severe lymphopenia. These pilot studies were conducted to determine the safety of this approach in mice and humans. METHODS: Ten BALB/c mice received focal brain irradiation (4Gy x 10 fractions). Half of the mice received intraperitoneal fingolimod (3mg/kg) before and during the two weeks of radiation. Five patients with newly diagnosed glioblastoma were given fingolimod one week prior to and during the six weeks of concurrent radiation and temozolomide. RESULTS: Mice treated with fingolimod and radiation had more severe lymphopenia than those treated with radiation alone. However, lymphocyte counts and weight loss recovered similarly in both treatment cohorts and no added toxicities were noted. Humans receiving fingolimod developed severe lymphopenia which deepened when radiation and temozolomide were initiated. This was well tolerated and no grade III-IV opportunistic infections were noted. CONCLUSIONS: These pilot studies demonstrate the feasibility and safety of combining fingolimod with radiation in mice and humans. This novel approach to reducing the number of circulating lymphocytes exposed to radiation deserves further study given the importance of the host immune system on cancer survival and response to immunologic interventions.

Elite controllers are human immunodeficiency virus-1–positive individuals capable of sustaining undetectable viral loads without treatment. We present the case of an elite controller diagnosed with extensive stage small cell lung cancer who maintained a viral load of <20 copies/mL despite the development of severe treatment-related lymphopenia.