Increasing the Dye Payload of Cetuximab-IRDye800CW Enables Photodynamic Therapy.

Cetuximab (Cet)-IRDye800CW, among other antibody-IRDye800CW conjugates, is a potentially effective tool for delineating tumor margins during fluorescence image-guided surgery (IGS). However, residual disease often leads to recurrence. Photodynamic therapy (PDT) following IGS is proposed as an approach to eliminate residual disease but suffers from a lack of molecular specificity for cancer cells. Antibody-targeted PDT offers a potential solution for this specificity problem. In this study, we show, for the first time, that Cet-IRDye800CW is capable of antibody-targeted PDT in vitro when the payload of dye molecules is increased from 2 (clinical version) to 11 per antibody. Cet-IRDye800CW (1:11) produces singlet oxygen, hydroxyl radicals, and peroxynitrite upon activation with 810 nm light. In vitro assays on FaDu head and neck cancer cells confirm that Cet-IRDye800CW (1:11) maintains cancer cell binding specificity and is capable of inducing up to ∼90% phototoxicity in FaDu cancer cells. The phototoxicity of Cet-IRDye800CW conjugates using 810 nm light follows a dye payload-dependent trend. Cet-IRDye800CW (1:11) is also found to be more phototoxic to FaDu cancer cells and less toxic in the dark than the approved chromophore indocyanine green, which can also act as a PDT agent. We propose that antibody-targeted PDT using high-payload Cet-IRDye800CW (1:11) could hold potential for eliminating residual disease postoperatively when using sustained illumination devices, such as fiber optic patches and implantable surgical bed balloon applicators. This approach could also potentially be applicable to a wide variety of resectable cancers that are amenable to IGS-PDT, using their respective approved full-length antibodies as a template for high-payload IRDye800CW conjugation.

Correlation of Bronchoscopy and CT in Characterizing Malignant Central Airway Obstruction.

BACKGROUND: Malignant Central Airway Obstruction (MCAO) presents a significant challenge in lung cancer management, with notable morbidity and mortality implications. While bronchoscopy is the established diagnostic standard for confirming MCAO and assessing obstruction subtype (intrinsic, extrinsic, mixed) and severity, Computed Tomography (CT) serves as an initial screening tool. However, the extent of agreement between CT and bronchoscopy findings for MCAO remains unclear. METHODS: To assess the correlation between bronchoscopy and CT, we conducted a retrospective review of 108 patients at Roswell Park Comprehensive Cancer Center, analyzing CT and bronchoscopy results to document MCAO presence, severity, and subtype. RESULTS: CT correctly identified MCAO in 99% of cases (107/108). Agreement regarding obstruction subtype (80.8%, Cohen's κ = 0.683, p < 0.001), and severity (65%, Quadratic κ = 0.657, p < 0.001) was moderate. CT tended to equally overestimate (7/19) and underestimate (7/19) the degree of obstruction. CT was also poor in identifying mucosal involvement in mixed MCAO. CONCLUSIONS: CT demonstrates reasonable agreement with bronchoscopy in detecting obstruction. Nevertheless, when CT indicates a positive finding for MCAO, it is advisable to conduct bronchoscopy. This is because CT lacks reliability in determining the severity of obstruction and identifying the mucosal component of mixed disease.

Epidemiology and Survival of Malignant Central Airway Obstruction in Lung Cancer Identified on Cross-Sectional Imaging.

BACKGROUND: The prevalence of malignant central airway obstruction at diagnosis and its 5-year incidence are largely unknown, as are basic epidemiological data pertaining to this serious condition. To address these data limitations, we retrospectively collected data from the cohort of patients diagnosed with lung cancer at our institution in 2015 and followed cohort patients 5 years forward, until 2020. METHODS: We reviewed index PET/CT or CT scans at the time of lung cancer diagnosis to identify the presence, subtype, and severity of malignant central airway obstruction as well as progression/development over the next 5 years. RESULTS: The prevalence of malignant central airway obstruction affecting the airway lumen by 25% or greater was 17%, and its 5-year incidence of development was 8.2%. Notable associations from the multivariate analysis included a younger age and a stepwise increase in obstruction with increasing stage of disease. Squamous cell carcinoma and small-cell lung cancer were the 2 histologic subtypes with the strongest association with obstruction. The presence of malignant central airway obstruction either at time of diagnosis or on follow-up imaging was associated with significantly shortened survival (multivariate Cox proportional HR for MCAO=1.702, P<0.001). CONCLUSION: This study provides the first systematic characterization of fundamental epidemiological data on malignant central airway obstructions at a tertiary cancer center in the United States. This data is important to inform research directions and funding efforts of this serious complication. It also serves as a baseline value against which to compare for future studies.