Association of tumor growth rate with overall survival and recurrence among patients with laryngeal squamous cell carcinoma.

BACKGROUND: Delay in time to treatment initiation (TTI) is associated with worsened survival outcomes in laryngeal squamous cell carcinoma (LSCC). It is unclear whether this is due to tumor growth or an increased risk of metastatic disease. METHODS: This retrospective cohort study at one academic center included patients with LSCC who underwent radiotherapy/chemoradiotherapy between 2005 and 2017. We examined the association between tumor growth rate (TGR) and survival outcomes. RESULTS: Among 105 patients (mean age, 63.8 ± 11.1 years; 72% male), the threshold between "slow-growing" and "fast-growing" tumors was >0.036 mL/day (survival) and >0.082 mL/day (recurrence). Faster growth was associated with worse overall survival (OS) (hazard ratio, 1.97; 95% confidence interval [CI], 0.94-4.13) and increased recurrence (odds ratio, 9.10; 95% CI, 2.40-34.4). CONCLUSIONS: TGR >0.036 mL/day during TTI was associated with decreased OS, and >0.082 mL/day was associated with increased recurrence. Tumor measurement in patients experiencing delay may identify those who could benefit from escalated therapy.

Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4-96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

Complications related to thyroidectomy among patients with hyperthyroidism: Exploring the potential for ambulatory surgery.

BACKGROUND: Total thyroidectomy for hyperthyroidism is typically followed by overnight admission to monitor for complications including thyrotoxicosis. Outpatient thyroid surgery is increasingly common, but its safety in patients with hyperthyroidism has not been well studied. METHODS: This retrospective study reviewed 183 patients with hyperthyroidism who underwent total thyroidectomy from 2015 to 2022 at one urban, academic center. The main outcomes were rates of thyroid storm, surgical complications, and 30-day ED visits and readmissions. RESULTS: Among 183 patients with hyperthyroidism (mean age, 45 ± 14.5 years; 82.5% female), there were no cases of thyroid storm and complications included recurrent laryngeal nerve (RLN) palsy (7.0%), symptomatic hypocalcemia (4.4%), and hematoma (1.6%). ED visits were present in 1.1% and no patients were readmitted. CONCLUSION: Total thyroidectomy was not associated with thyroid storm and <6% of patients required inpatient management. Ambulatory total thyroidectomy for hyperthyroidism warrants further consideration through identification of predictive factors for postoperative complications.

Characterization of a Diverse Set of Conditionally Reprogrammed Head and Neck Cancer Cell Cultures.

OBJECTIVE: To establish and characterize a diverse library of head and neck squamous cell cancer (HNSCC) cultures using conditional reprogramming (CR). METHODS: Patients enrolled on an IRB-approved protocol to generate tumor cell cultures using CR methods. Tumor and blood samples were collected and clinical information was recorded. Successful CR cultures were validated against banked reference tumors with short tandem repeat genotyping. Cell morphology was archived with photodocumentation. Clinical and demographic factors were evaluated for associations with successful establishment of CR culture. Human papilloma virus (HPV) genotyping, clonogenic survival, MTT assays, spheroid growth, and whole exome sequencing were carried out in selected cultures. RESULTS: Forty four patients were enrolled, with 31 (70%) successful CR cultures, 32% derived from patients who identified as Black and 61% as Hispanic. All major head and neck disease sites were represented, including 15 (48%) oral cavity and 8 (26%) p16-positive oropharynx cancers. Hispanic ethnicity and first primary tumors (vs. second primary or recurrent tumors) were significantly associated with successful CR culture. HPV expression was conserved in CR cultures, including CR-024, which carried a novel HPV-69 serotype. CR cultures were used to test cisplatin responses using MTT assays. Previous work has also demonstrated these models can be used to assess response to radiation and can be engrafted in mouse models. Whole exome sequencing demonstrated that CR cultures preserved tumor mutation burden and driver mutations. CONCLUSION: CR culture is highly successful in propagating HNSCC cells. This study included a high proportion of patients from underrepresented minority groups. LEVEL OF EVIDENCE: Not Applicable Laryngoscope, 134:2748-2756, 2024.