Faculty Bibliography

Multiplexed immunofluorescence imaging allows the multidimensional molecular profiling of cellular environments at subcellular resolution. However, identifying and characterizing disease-relevant microenvironments from these rich datasets is challenging. Here we show that a graph neural network that leverages spatial protein profiles in tissue specimens to model tumour microenvironments as local subgraphs captures distinctive cellular interactions associated with differential clinical outcomes. We applied this spatial cellular-graph strategy to specimens of human head-and-neck and colorectal cancers assayed with 40-plex immunofluorescence imaging to identify spatial motifs associated with cancer recurrence and with patient survival after treatment. The graph deep learning model was substantially more accurate in predicting patient outcomes than deep learning approaches that model spatial data on the basis of the local composition of cell types, and it generated insights into the effect of the spatial compartmentalization of tumour cells and granulocytes on patient prognosis. Local graphs may also aid in the analysis of disease-relevant motifs in histology samples characterized via spatial transcriptomics and other -omics techniques.

BACKGROUND:Transoral robotic surgery (TORS) is an emerging minimally invasive surgical treatment for residual, recurrent, and new primary head and neck cancers in previously irradiated fields, with limited evidence for its oncological effectiveness. METHODS:A retrospective observational cohort study of consecutive cases performed in 16 high-volume international centers before August 2018 was conducted (registered at clinicaltrials.gov [NCT04673929] as the RECUT study). Overall survival (OS), disease-free survival, disease-specific survivals (DSS), and local control (LC) were calculated using Kaplan-Meier estimates, with subgroups compared using log-rank tests and Cox proportional hazards modeling for multivariable analysis. Maximally selected rank statistics determined the cut point for closest surgical resection margin based on LC. RESULTS:Data for 278 eligible patients were analyzed, with median follow-up of 38.5 months. Two-year and 5-year outcomes were 69.0% and 62.2% for LC, 71.8% and 49.8% for OS, 47.2% and 35.7% for disease-free survival, and 78.7% and 59.1% for disease-specific survivals. The most discriminating margin cut point was 1.0 mm; the 2-year LC was 80.9% above and 54.2% below or equal to 1.0 mm. Increasing age, current smoking, primary tumor classification, and narrow surgical margins (≤1.0 mm) were statistically significantly associated with lower OS. Hemorrhage with return to theater was seen in 8.1% (n = 22 of 272), and 30-day mortality was 1.8% (n = 5 of 272). At 1 year, 10.8% (n = 21 of 195) used tracheostomies, 33.8% (n = 66 of 195) used gastrostomies, and 66.3% (n = 53 of 80) had maintained or improved normalcy of diet scores. CONCLUSIONS:Data from international centers show TORS to treat head and neck cancers in previously irradiated fields yields favorable outcomes for LC and survival. Where feasible, TORS should be considered the preferred surgical treatment in the salvage setting.

OBJECTIVES/HYPOTHESIS:Hashimoto's Thyroiditis (HT) is a common cause of hypothyroidism. Among adults with differentiated thyroid cancer (DTC), HT appears to be associated with less severe disease burden. In the absence of information regarding HT and disease burden among children with DTC, we assessed the relationship between pediatric DTC severity and HT. STUDY DESIGN:Retrospective cohort. METHODS:Charts from 90 pediatric patients who underwent surgical removal of DTC from 2002 to 2017 at tertiary-care children's hospital were reviewed. Demographic, clinical, surgical, pathology, and outcome details were compared between patients with and without HT. Consistency among diagnostic modalities of HT was also evaluated. RESULTS:Median age at presentation was 16.0 years (range 4.2-18.9 years). Twenty-two patients were male (24%). Forty-five patients (50%) had HT based on presence of thyroid autoantibodies and/or surgical pathology findings and 45 patients did not have HT. Patients with HT had increased odds of microcalcifications (odds ratio [OR]: 3.01, P = .031) and decreased odds of palpable nodules (OR: 0.212, P = .024) and T2 lesions (vs. T1) (OR: 0.261, P = .015) compared with non-HT. No significant differences in demographics and the incidence of multifocality, extrathyroidal extension, lymphovascular invasion, lymph node or pulmonary metastases, disease recurrence, or radioactive iodine treatment were found between the two groups. Thyroglobulin/thyroid peroxidase autoantibodies and surgical pathology indicative of HT were concordant in 82.4% (κ = 0.635, P < .001). CONCLUSION:HT was present in 50% of children with DTC. Patients with DTC and HT presented with smaller tumors compared to non-HT patients. No significant differences in other markers of disease aggressiveness were found between the two groups. LEVEL OF EVIDENCE:3 Laryngoscope, 132:1668-1674, 2022.

OBJECTIVES/UNASSIGNED:Data on the efficacy of including definitive local therapy to the primary site for head and neck squamous cell carcinoma (HNSCC) patients with synchronous distant metastasis are lacking. In multiple different solid tumor types, there has been benefit when using systemic therapy followed by local consolidative therapy (stereotactic ablative radiotherapy or surgery) directed at metastases. We proposed to retrospectively evaluate patients at our institution that received definitive treatment to the primary. METHODS/UNASSIGNED:Single institution retrospective study evaluating 40 patients with metastatic HNSCC treated with definitive surgery (55%) or chemoradiation (45%) to the primary site from 2000 to 2020. The major endpoints were overall survival (OS) and progression-free survival (PFS) for the total population and multiple sub-groups. Some variables were evaluated with multiple covariates Cox model. RESULTS/UNASSIGNED:The median PFS was 8.6 months (95% CI, 6.4-11.6), and OS was 14.2 months (95% CI, 10.9-27.5). In 28% of patients that received induction therapy, there was a twofold increase in median overall survival to 27.5 months. In the 33% of patients that received anti-PD-1 mAb as part of their treatment course, the median OS was significantly increased to 41.7 months (95% CI, 8.7-NR) versus 12.1 months (95% CI, 8.4-14.4) with a 5-year OS of 39%. Multivariate analysis for OS showed significance for age at diagnosis, use of IO, and number of metastatic sites. CONCLUSION/UNASSIGNED:We observed impressive survival outcomes in metastatic HNSCC patients treated with definitive local therapy to the primary site in addition to induction and/or immunotherapy. Further study is warranted.Level of Evidence: 3.