Paniello, Randal C.

PURPOSE The volume treated with postoperative radiation therapy (PORT) is a mediator of toxicity, and reduced volumes result in improved quality of life (QOL). In this phase II trial, treatment volumes were reduced by omitting PORT to the pathologically negative (PN0) neck in patients with primary head and neck squamous cell carcinoma. METHODS Patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection with a PN0 neck and high-risk features mandating PORT to the primary and/or involved neck were eligible. The primary end point was greater than 90% disease control in the unirradiated neck. QOL was evaluated using the MD Anderson Dysphagia Inventory and the University of Michigan patient-reported xerostomia questionnaire. RESULTS Seventy-three patients were enrolled, and 72 were evaluable. Median age was 56 years (range, 31 to 81 years); 58 patients were male, and 47 (65%) had a smoking history. Sites included oral cavity (n = 14), oropharynx (n = 37), hypopharynx (n = 4), larynx (n = 16), and unknown primary tumor (n = 1). According to the American Joint Committee on Cancer Staging Manual (7 th edition), 67 patients (93%) had stage III/IV disease, and 71% of tumors involved or crossed midline. No patient had contralateral neck PORT. In 17 patients (24%), only the primary site was treated. At a median follow-up of 53 months, two patients experienced treatment failure of the PN0 unirradiated neck; they also experienced treatment failure locally. Unirradiated neck control was 97% (95% CI, 93.4% to 100.0%). Five-year rates of local control, regional control, progression-free survival, and overall survival were 84%, 93%, 60%, and 64%, respectively. QOL measures were not significantly different from baseline at 12 and 24 months post-PORT ( P > .05). CONCLUSION Eliminating PORT to the PN0 neck resulted in excellent control rates in the unirradiated neck without long-term adverse effects on global QOL.

Objectives/HypothesisTo evaluate outcomes for patients with pathological N3 (pN3) neck disease from human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma (OPSCC) and determine variables predictive of survival.Study DesignRetrospective case series with chart review.MethodsThis study was conducted between 1998 and 2013 and included patients with HPV‐related OPSCC treated with surgery with or without adjuvant therapy and who had pN3 nodal disease. The primary outcome was disease‐specific survival (DSS). Secondary outcomes included overall survival (OS), disease‐free survival (DFS), adverse events, and gastrostomy tube rates.ResultsThirty‐nine patients were included, of whom 36 (90%) underwent adjuvant therapy. Median follow‐up was 39 months (range, 2–147 months). Mean age was 56 years, and 87% were male. Seventeen patients (44%) underwent selective neck dissection, whereas six (15%) underwent radical (n = 2) or extended radical (n = 4) neck dissection. Ninety‐two percent had extracapsular extension. Five‐year Kaplan‐Meier estimated DSS, OS, and DFS were 89% (95% confidence interval [CI]: 79%–99%), 87% (95% CI: 75%–99%), and 84% (95% CI: 72%–96%), respectively. The disease recurrence rate was 10% (5% regional, 5% distant metastasis). Patients with less than 5 pathologically positive lymph nodes (P = .041) had improved DFS.ConclusionsPatients with HPV‐related OPSCC and pN3 nodal disease treated with surgery and adjuvant therapy have very favorable long‐term survival and regional control. Patients with five or more pathologically positive lymph nodes may be at higher risk for recurrence.Level of Evidence4. Laryngoscope, 127:2033–2037, 2017

AbstractAlthough coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult‐onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P < 0.01). Dystonia classification included cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw‐opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult‐onset primary dystonia.