Background To report associations between p16 status, clinicopathologic characteristics, and outcomes for unknown primary head and neck squamous cell carcinoma (SCCUPS). Methods Specimens of SCCUPS were re-analyzed. HPV status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in HNSCC. Results A majority of the population (n = 26, 74%) was p16+. Prognostic factors benefitting survival were p16+ status (p < 0.0001), absence of macroscopic extracapsular extension [ECE] (p = 0.004), younger age (p = 0.01), and higher grade (p = 0.007). The prognostic implication of worse OS with macroscopic ECE (p = 0.009) remained significant when limited to p16+ patients (p=0.002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between SCCUPS and known-primary cancer. Conclusions The majority of SCCUPS patients were p16+, indicative of HPV association. p16 staining and ECE appear to be the most prognostic features in SCCUPS.

It has been reported that the photo-oxidation of A2E, a component of human retinal lipofuscin, leads to products that are toxic to cells via dark reactions. Because these compounds have been implicated in the development of various maculopathies such as age-related macular degeneration (AMD), it is important to determine the structures of those deleterious compounds. Both the photo-oxidation and auto-oxidation of A2E lead to the same complex mixture of products, some of which have lower molecular weights than the staring material. Because A2E is homologous to beta-carotene, it was hypothesized that its oxidation would lead to products analogous to those found in oxidized beta-carotene, namely, a series of cleavage products along the acyclic chain with the concomitant formation of aldehydes. This was found to be the case based upon 1) the formation of all of the aldehydes predicted from the oxidation of beta-carotene, 2) the loss of 28 amu (carbonyl moiety) from the molecular ion, 3) the facile reaction of the aldehydes with nitrophenylhydrazines to form nitrophenylhydrazones and 4) the subsequent MS/MS cleavage of those derivatives at the N-N bond. If formed in vivo, these aldehydes would have toxic effects on any cell. Finally, the similarity in product mixtures from both the photo-oxidation and auto-oxidation strongly suggests that the intermolecular photo-oxidation of A2E results primarily from a radical process without the involvement of singlet oxygen. Any formation of singlet oxygen most likely arises from sensitization by the aldehyde oxidation products, as this process is well known for aldehydes, in general, and retinal, specifically.

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Purpose/Objective(s) Conformal radiation therapy in the post-prostatectomy setting requires accurate setup and localization of the prostatic fossa. In this series, we report prostate bed localization and motion characteristics using data collected from implanted radiofrequency transponders. Materials and Methods The Calypso 4D Localization System uses three implanted radiofrequency transponders for daily target localization and real-time tracking throughout a course of radiation therapy. We reviewed the localization and tracking reports of 20 patients who received ultrasound-guided placement of Calypso transponders within the prostate bed prior to a course of intensity modulated radiation therapy at Fox Chase Cancer Center. Results At localization, prostate bed displacement relative to bony anatomy exceeded 5 mm in 9% of fractions in the Anterior-Posterior (A-P) direction, and 21% of fractions in the Superior-Inferior (S-I) direction. The three-dimensional vector length from skin marks to Calypso alignment exceeded 1 cm in 24% of all 652 fractions with available setup data. During treatment, the target exceeded the 5 mm tracking limit for at least 30 seconds in 11% of all fractions, generally in the A-P or S-I directions. In the A-P direction, target motion was twice as likely to move posteriorly, towards the rectum, than anteriorly. 15% of all treatments were interrupted for repositioning, and 70% of patients were repositioned at least once during their treatment course. Conclusion Set-up errors and motion of the prostatic fossa during radiotherapy are nontrivial, leading to potential undertreatment of target and excess normal tissue toxicity if not taken into account during treatment planning. Localization and real-time tracking of the prostate bed via implanted Calypso transponders can be used to improve the accuracy of plan delivery.