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Purpose: Platinum-based chemotherapy with or without immunotherapy is the mainstay of treatment for advanced stage non-small cell lung cancer (NSCLC) lacking a molecular driver alteration. Pre-clinical studies have reported that pharmacological ascorbate (P-AscH-) enhances NSCLC response to platinum-based therapy. We conducted a phase II clinical trial combining P-AscH- with carboplatin-paclitaxel chemotherapy., Experimental Design: Chemotherapy naïve advanced stage NSCLC patients received 75 g ascorbate twice per week intravenously with carboplatin and paclitaxel every three weeks for four cycles. The primary endpoint was to improve tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 compared to the historical control of 20%. The trial was conducted as an optimal Simon's two-stage design. Blood samples were collected for exploratory analyses., Results: The study enrolled 38 patients and met its primary endpoint with an objective response rate of 34.2% (p = 0.03). All were confirmed partial responses (cPR). The disease control rate was 84.2% (stable disease + cPR). Median progression-free and overall survival were 5.7 months and 12.8 months, respectively. Treatment-related adverse events (TRAE) included one grade 5 (neutropenic fever) and five grade 4 events (cytopenias). Cytokine and chemokine data suggest that the combination elicits an immune response. Immunophenotyping of peripheral blood mononuclear cells demonstrated an increase in effector CD8 T-cells in patients with a progression-free survival (PFS) ≥ 6 months., Conclusions: The addition of P-AscH- to platinum-based chemotherapy improved tumor response in advanced stage NSCLC. P-AscH- appears to alter the host immune response and needs further investigation as a potential adjuvant to immunotherapy., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Patients with small node-negative breast tumors who are younger or who have human epidermal growth factor receptor 2-positive (HER2(+)) or triple-negative breast cancer (TNBC) subtypes are at increased risk of recurrence. Concurrently, systemic treatment recommendations have evolved. Less is known about how frequently cytotoxic chemotherapy is given to these patients. Mastectomy rates have also increased. This study reports the recent incidence of T1a,bN0M0 breast cancer and the characteristics associated with chemotherapy delivery and the surgery selected., Patients and Methods: This retrospective cohort is composed of invasive female breast cancers diagnosed with American Joint Committee on Cancer (AJCC) stage T1a,bN0M0 during 2010 to 2012 from the Iowa Surveillance, Epidemiology, and End Results (SEER) Cancer Registry. Chemotherapy use and surgery were identified by the registry. Univariate and multivariate analyses were performed to determine patient differences across subtype and factors associated with treatment., Results: The study included 1687 patients. This represented 27.6% of all AJCC stages I(a-c) to III breast cancer in 2010 to 2012, up from 18% in 1990 (P < .0001). Of 1456 patients with known subtype, 8.8% and 6.4% had HER2(+) and TNBC disease, respectively. Chemotherapy was given to 7.5% of women with T1aN0M0 and 12.7% of T1bN0M0 tumors. The likelihood of systemic treatment was associated with breast cancer subtype, tumor differentiation, and age in a multivariate model. The mastectomy rate was 31.8%., Conclusion: Small node-negative breast cancers continue to grow significantly as a percentage of invasive breast cancer diagnoses. In 2010 to 2012 in Iowa, systemic chemotherapy correlated with risk factors associated with recurrence: age, subtype, and tumor differentiation. Relatively high rates of mastectomy were seen., (Copyright © 2015 Elsevier Inc. All rights reserved.)