Gerndt, Sophie P.

Abstract Purpose: Relapse is a major cause of failure in human papillomavirus–independent head and neck squamous cell carcinoma. Clinicopathologic criteria for adjuvant treatment remain imprecise and have not changed for decades. We investigated whether ctDNA in lymphatic exudate collected via surgical drains (“lymph”) 24 hours after surgery identified molecular residual disease (MRD) and compared its performance with time-matched plasma. Experimental Design: Using an ultra-sensitive tumor-informed sequencing approach, tumor variants were called in lymph and plasma to classify patients as ctDNA positive or ctDNA negative, trained in an initial cohort of 36 patients, and replicated in an independent cohort of 37 patients. Progression-free survival was compared in ctDNA(+) versus ctDNA(–) patients. Results: Lymph identified MRD in two independent multi-site cohorts (initial cohort sensitivity = 76% and specificity = 63%; log-rank P = 0.01; replication cohort sensitivity = 65% and specificity = 70%; log-rank P = 0.04). Lymph performance was enhanced in locoregional relapse (sensitivity = 78% and specificity = 67%; log-rank P = 0.0004) and generalized to early-stage patients. Analysis of matched plasma collected at this early timepoint was not predictive of recurrence (sensitivity = 35% and specificity = 72%; log-rank P = 0.7). In patients with intermediate-risk pathology, lymph ctDNA was associated with recurrence (sensitivity = 88% and specificity = 67%; log-rank P = 0.0008), suggesting an opportunity for improved stratification of patients who may benefit from additional adjuvant treatment. Conclusions: Postoperative lymph is a novel, proximal, and early source of MRD with the potential to introduce more precision into adjuvant therapy decision-making and improve outcomes, especially for patients with intermediate-risk human papillomavirus–independent head and neck squamous cell carcinoma.

Given the high prevalence of otolaryngology infections such as tonsillitis, otitis, and pharyngitis in low and middle income countries, the field of global otolaryngology continues to grow to accommodate patients around the world. This commentary focuses on best practices in transcultural communications between US doctors and foreign patients with an emphasis on cultural competency. We use alternative medicine as an exemplar for how to collaborate with patients to develop treatment plans that respect their cultural beliefs and lifestyles. Rather than assigning value to the patient’s alternative medicine practices, we believe that instructing and counseling a patient on how to incorporate follow‐up visits and rehabilitation after allopathic medical procedures such as surgical tonsillectomy should be done in a way that respects the patient’s preexisting health regimen. By doing so, these new aspects of their health care will take a discrete place in their wellness practices and engender more trust and better health outcomes.