A Phase Ib Study of Preoperative, Locoregional IRX-2 Cytokine Immunotherapy to Prime Immune Responses in Patients with Early-Stage Breast Cancer.

PURPOSE: To evaluate the safety and feasibility of preoperative locoregional cytokine therapy (IRX-2 regimen) in early-stage breast cancer, and to evaluate for intratumoral and peripheral immunomodulatory activity. PATIENTS AND METHODS: Sixteen patients with stage I-III early-stage breast cancer (any histology type) indicated for surgical lumpectomy or mastectomy were enrolled to receive preoperative locoregional immunotherapy with the IRX-2 cytokine biological (2 mL subcutaneous × 10 days to periareolar skin). The regimen also included single-dose cyclophosphamide (300 mg/m2) on day 1 to deplete T-regulatory cells and oral indomethacin to modulate suppressive myeloid subpopulations. The primary objective was to evaluate feasibility (i.e., receipt of therapy without surgical delays or grade 3/4 treatment-related adverse events). The secondary objective was to evaluate changes in stromal tumor-infiltrating lymphocyte score. The exploratory objective was to identify candidate pharmacodynamic changes for future study using a variety of assays, including flow cytometry, RNA and T-cell receptor DNA sequencing, and multispectral immunofluorescence. RESULTS: Preoperative locoregional cytokine administration was feasible in 100% (n = 16/16) of subjects and associated with increases in stromal tumor-infiltrating lymphocytes (P < 0.001). Programmed death ligand 1 (CD274) was upregulated at the RNA (P < 0.01) and protein level [by Ventana PD-L1 (SP142) and immunofluorescence]. Other immunomodulatory effects included upregulation of RNA signatures of T-cell activation and recruitment and cyclophosphamide-related peripheral T-regulatory cell depletion. CONCLUSIONS: IRX-2 is safe in early-stage breast cancer. Potentially favorable immunomodulatory changes were observed, supporting further study of IRX-2 in early-stage breast cancer and other malignancies.

Radiation recall myelitis following paclitaxel chemotherapy: The first reported case.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) of the spine has become an increasingly utilized modality in the United States, most commonly for metastatic disease (McClelland et al., 2017). Spinal SBRT in patients with spinal instrumentation has been sparsely examined. We report a patient who developed myelitis following spinal SBRT to a region with existing hardware. METHODS: A 55-year-old woman with Stage IV breast cancer developed a T4 vertebral body metastasis and underwent tumor debulking with posteriorly instrumented T3-T5 fusion. Postoperatively she proceeded with SBRT to the T3-T5 vertebral bodies, receiving 30 Gy in 6 Gy/fraction. Seven months later, she required paclitaxel chemotherapy (80 mg/m2 per cycle) for new liver metastases. RESULTS: Eight months following spine SBRT, four weeks after having started chemotherapy she developed intractable back pain and right lower extremity numbness which improved upon receiving steroids for weekly chemotherapy; the numbness subsequently spread to her left leg. Thoracic spine MRI revealed a 1.7 cm ovoid focus of T4-T5 spinal cord enhancement with extensive surrounding cord edema extending superiorly to C6-C7, consistent with radiation myelitis. Hyperbaric oxygen moderately improved her symptoms; fortunately, she never developed motor symptomatology or bowel/bladder dysfunction. Thorough re-evaluation of the original thoracic spine SBRT plan revealed no deviations from the standard of care, nor did re-planning with alternate treatment planning software demonstrate any significant difference in maximum cord dosage than the original plan. CONCLUSIONS: The timing of symptomatology related to chemotherapy administration is consistent with radiation recall myelitis, which has yet to be reported following SBRT. Given the potentially disastrous consequences of myelitis, patients with metastatic disease previously treated with spine SBRT may be susceptible to developing myelitis if treated with paclitaxel chemotherapy.