Background Anti-PD-1 immune checkpoint blockade is approved for first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but few patients respond. Statin drugs (HMG-CoA reductase inhibitors) are associated with superior survival in several cancer types, including HNSCC. Emerging data suggest that manipulation of cholesterol may enhance some aspects of antitumor immunity. Methods We used syngeneic murine models (mouse oral cancer, MOC1 and TC-1) to investigate our hypothesis that a subset of statin drugs would enhance antitumor immunity and delay tumor growth. Results Using an ex vivo coculture assay of murine cancer cells and tumor infiltrating lymphocytes, we discovered that all seven statin drugs inhibited tumor cell proliferation. Simvastatin and lovastatin also enhanced T-cell killing of tumor cells. In mice, daily oral simvastatin or lovastatin enhanced tumor control and extended survival when combined with PD-1 blockade, with rejection of MOC1 tumors in 30% of mice treated with lovastatin plus anti-PD-1. Results from flow cytometry of tumors and tumor-draining lymph nodes suggested T cell activation and shifts from M2 to M1 macrophage predominance as potential mechanisms of combination therapy. Conclusions These results suggest that statins deserve further study as well-tolerated, inexpensive drugs that may enhance responses to PD-1 checkpoint blockade and other immunotherapies for HNSCC.

BACKGROUND. Cisplatin is widely used to treat adult and pediatric cancers. It is the most ototoxic drug in clinical use, resulting in permanent hearing loss in approximately 50% of treated patients. There is a major need for therapies that prevent cisplatin-induced hearing loss. Studies in mice suggest that concurrent use of statins reduces cisplatin-induced hearing loss. METHODS. We examined hearing thresholds from 277 adults treated with cisplatin for head and neck cancer. Pretreatment and posttreatment audiograms were collected within 90 days of initiation and completion of cisplatin therapy. The primary outcome measure was a change in hearing as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). RESULTS. Among patients on concurrent atorvastatin, 9.7% experienced a CTCAE grade 2 or higher cisplatin-induced hearing loss compared with 29.4% in nonstatin users (P < 0.0001). A mixed-effect model analysis showed that atorvastatin use was significantly associated with reduced cisplatin-induced hearing loss (P ≤ 0.01). An adjusted odds ratio (OR) analysis indicated that an atorvastatin user is 53% less likely to acquire a cisplatin-induced hearing loss than a nonstatin user (OR = 0.47; 95% CI, 0.30–0.78). Three-year survival rates were not different between atorvastatin users and nonstatin users (P > 0.05). CONCLUSIONS. Our data indicate that atorvastatin use is associated with reduced incidence and severity of cisplatin-induced hearing loss in adults being treated for head and neck cancer. TRIAL REGISTRATION. ClinicalTrials.gov identifier NCT03225157. FUNDING. Funding was provided by the Division of Intramural Research at the National Institute on Deafness and Other Communication Disorders (1 ZIA DC000079, ZIA DC000090).

Background: To achieve equitable access to cancer clinical trials (CCTs), patients must overcome structural, clinical, and attitudinal barriers to trial enrollment. The goal of this systematic review was to study the relationship between socioeconomic status (SES), assessed either by direct or proxy measures, and CCT enrollment.Methods: The review team and medical librarian developed search strategies for each database to identify studies for this systematic review, which was conducted according to PRISMA guidelines. Inclusion criteria were as follows: studies published in relevant scientific journals between January 2000 and July 2022, primary sources, English literature, and studies conducted in the US. Sixteen studies fulfilled the inclusion criteria and were reviewed. The risk of bias assessment was conducted independently by two reviewers using the Newcastle Ottawa scale.Results: The initial search yielded 4070 citations, and 16 studies were included in our review. Four of the studies included used patient reported annual income as a measure of SES, while the remaining 12 studies used patient zip code as a proxy measurement of SES. Consistent with our hypothesis, 13 studies showed a positive association between high SES (patient‐reported or proxy measurement) and CCT enrollment. Two studies showed a negative association, and one study showed no relationship.Conclusions: The existing literature suggests that low SES is associated with lower participation in CCT. The small number of studies identified on this topic highlights the need for additional research on SES and other barriers to CCT participation.

Objective: Review of the literature regarding hearing loss in patients with head and neck cancer treated with chemoradiation. Design: Studies in the literature are reviewed that pertain to hearing loss sustained in head and neck cancer patients receiving cisplatin-based chemoradiation. Personal observations noted while treating these patients are also detailed. Study sample: PubMed was searched for pertinent articles regarding hearing loss in head and neck cancer patients receiving cisplatin chemotherapy and/or radiation. Results: Studies on the incidence and severity of hearing loss in head and neck cancer patients are limited, but those studies suggest that the risk of hearing loss is greater with higher-dose regimens. Conclusions: Newer cisplatin chemotherapy regimens using lower, weekly doses may be associated with a lower incidence and severity of hearing loss; however, large prospective studies are needed. Such information will be paramount to effective pre-treatment counselling of head and neck cancer patients.