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Different methodologies to deliver craniospinal irradiation (CSI) to patients have been implemented due to the toxicity and planning challenges associated with traditional three-dimensional conformal radiation therapy. Patient outcomes data are needed to assess the feasibility and safety of these methods. We describe the set up and planning methodology used in our clinic to treat adult patients undergoing CSI using volumetric-modulated arc therapy (VMAT). Eight patients treated with CSI using VMAT delivery were reviewed for treatment-associated toxicities and survival. Median follow-up time was 7.5 months (range 1–44 months), and median radiation dose was 36 Gy (range 23.4–36 Gy). The most common acute toxicities experienced were nausea (n= 5, 62.5%), fatigue (n= 4, 50%), and sore throat (n= 3, 37.5%). Grade III toxicities included leukopenia (n= 2, 25%), fatigue (n= 1, 12.5%), anemia (n= 1, 12.5%), and nausea (n= 1, 12.5%). There were no grade IV or V toxicities. Only patients receiving adjuvant chemotherapy (n= 2) had hematologic toxicities (grade II anemia, n= 1; grade III anemia n= 1; grade III leukopenia, n= 2). VMAT radiation delivery is feasible and well tolerated in adult patients receiving CSI. The addition of adjuvant chemotherapy carries an increased risk for hematologic toxicity.

We previously isolated an IL-11–mimic motif (CGRRAGGSC) that binds to IL-11 receptor (IL-11R) in vitroand accumulates in IL-11R–expressing tumors in vivo. This synthetic peptide ligand was used as a tumor-targeting moiety in the rational design of BMTP-11, which is a drug candidate in clinical trials. Here, we investigated the specificity and accessibility of IL-11R as a target and the efficacy of BMTP-11 as a ligand-targeted drug in lung cancer. We observed high IL-11R expression levels in a large cohort of patients (n = 368). In matching surgical specimens (i.e., paired tumors and nonmalignant tissues), the cytoplasmic levels of IL-11R in tumor areas were significantly higher than in nonmalignant tissues (n = 36; P = 0.003). Notably, marked overexpression of IL-11R was observed in both tumor epithelial and vascular endothelial cell membranes (n = 301; P < 0.0001). BMTP-11 induced in vitrocell death in a representative panel of human lung cancer cell lines. BMTP-11 treatment attenuated the growth of subcutaneous xenografts and reduced the number of pulmonary tumors after tail vein injection of human lung cancer cells in mice. Our findings validate BMTP-11 as a pharmacologic candidate drug in preclinical models of lung cancer and patient-derived tumors. Moreover, the high expression level in patients with non-small cell lung cancer is a promising feature for potential translational applications.