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Importance Lower cranial neuropathy (LCNP) is a rare but potentially disabling result of radiotherapy and other head and neck cancer therapies. Survivors who develop late LCNP may experience profound functional impairment, with deficits in swallowing, speech, and voice. Objective To investigate the association of late LCNP with severity of cancer treatment–related symptoms and subsequent general functional impairment among oropharyngeal cancer (OPC) survivors. Design, Setting, and Participants This cross-sectional survey study analyzed 889 OPC survivors nested within a retrospective cohort of OPC survivors treated at MD Anderson Cancer Center from January 1, 2000, to December 31, 2013. Eligible survey participants were disease free and completed OPC treatment 1 year or more before the survey. Data analysis was performed from October 10, 2017, to March 15, 2018. Exposures Late LCNP defined by onset 3 months or more after cancer therapy. Main Outcomes and Measures The primary outcome variable was the mean of the top 5 most severely scored symptoms of all 22 core and head and neck cancer–specific symptoms from the MD Anderson Symptom Inventory Head and Neck Cancer Module (MDASI-HN). Secondary outcomes included mean MDASI-HN interference scores and single-item scores of the most severe symptoms. Multivariate models regressed MDASI-HN scores on late LCNP status, adjusting for clinical covariates. Results Overall, 36 of 889 OPC survivors (4.0%) (753 [84.7%] male; 821 [92.4%] white; median [range] age, 56 [32-84] years; median [range] survival time, 7 [1-16] years) developed late LCNP. Late LCNP was significantly associated with worse mean top 5 MDASI-HN symptom scores (coefficient, 1.54; 95% CI, 0.82-2.26), adjusting for age, survival time, sex, therapeutic modality, T stage, subsite, type of radiotherapy, smoking, and normal diet before treatment. Late LCNP was also significantly associated with single-item scores for difficulty swallowing or chewing (coefficient, 2.25; 95% CI, 1.33-3.18), mucus (coefficient, 1.97; 95% CI, 1.03-2.91), fatigue (coefficient, 1.35; 95% CI, 0.40-2.21), choking (coefficient, 1.53; 95% CI, 0.65-2.41), and voice or speech symptoms (coefficient, 2.30; 95% CI, 1.60-3.03) in multivariable models. Late LCNP was not significantly associated with mean interference scores after correction for multiple comparisons (mean interference coefficient, 0.72; 95% CI, 0.09-1.35). Conclusions and Relevance In this large survey study, OPC survivors with late LCNP reported worse cancer treatment–related symptoms, a finding suggesting an association between late LCNP and symptom burden. This research may inform the development and implementation of strategies for LCNP surveillance and management.

Objective To review the oncologic outcomes in patients with advanced (stage III-IV) squamous cell carcinoma of the paranasal sinuses treated with induction chemotherapy prior to definitive local therapy. Methods The medical records of 46 consecutive patients with previously untreated, biopsy-proved squamous cell carcinoma of the paranasal sinuses who received induction chemotherapy during the course of their treatment were reviewed for demographics, tumor types and stages, treatment details, and oncologic outcomes. Results Of the 46 patients (median age, 59 years), the tumor epicenter was in the maxillary sinus in 31 (67%), ethmoid sinus in 9 (20%), nasal cavity in 4 (9%), and sphenoid sinus in 2 (4%). All patients had T3 or T4 tumors, and 12 (26%) patients had clinical evidence of nodal metastasis, with an overall stage of III (20%) or IV (80%). Induction chemotherapy regimens consisted of a combination of a taxane and platinum in 80% of patients, by themselves (14 patients) or in combination with a third agent, such as ifosfamide (14 patients) or 5-fluorouracil (9 patients). The combination of a taxane and 5-fluorouracil was used in the remaining 9 patients. More than two-thirds (67%) of the patients achieved at least a partial response to induction chemotherapy, 24% had progressive disease, and 9% had stable disease. Subsequent treatment after induction chemotherapy consisted of surgery, usually followed by radiation or chemoradiation or by definitive radiation or chemoradiation with surgical salvage of any residual disease. Overall, surgical resection was performed in only 24 of 46 patients (52%) treated with induction chemotherapy. The 2-year survival for patients with at least a partial response or stable disease after induction chemotherapy was 77% in contrast to only 36% for patients with progressive disease. Conclusions Tumor response to induction chemotherapy in patients with advanced squamous cell carcinoma of the paranasal sinuses may be predictive of treatment outcome and prognosis. Favorable response to induction chemotherapy is associated with better survival and a reasonable chance of organ preservation.

Background: Saliva is a readily accessible secretion that may be used in the diagnosis and screening of patients with head and neck squamous cell carcinoma (HNSCC). Methods: Saliva from 5 healthy volunteers and 3 patients with oral squamous cell carcinomas was used for proteomic analysis; we first depleted major proteins by affinity column. Depleted saliva was then divided and analyzed by the following methods: (1) liquid chromatography-tamden mass spectrometric (LC-MS/MS) after insolution digestion and peptide anion exchange chromatography, (2) peptide separation by chromatography, and (3) sodium dodecyl sulfate–polyacrylamide gel electrophoresis and in-gel digestion and liquid chromatography/tandem mass spectrometry. Results: Method 1 identified 14 to 44 proteins in all normal samples. Method 2 identified 21 to 118 proteins, and method 3 identified 64 to 163 proteins. Proteins present in all normal samples were 4, 11, and 26 for methods 1, 2, and 3, respectively. Unique proteins 33, 14, and 33 were identified in patients’ saliva for each sample. Compared with normal saliva, the saliva of patients with SCC contained 2 unique proteins: alpha-1-B-glycoprotein and complement factor-B. These proteins can be targeted for future validation in clinical trials. Conclusions: (1) A set of common proteins is identified among all normal saliva samples. (2) Intermethodological differences between specimens were noted. (3) Certain distinctive proteins distinguish normal saliva from saliva of subjects with HNSCC. (4) Saliva is an easy and accessible source for diagnosis and screening of HNSCC.

Background Aggressive nonmelanoma skin cancer (ANMSC) of the head and neck may require parotidectomy because of neurotropic spread, direct invasion of the parotid gland, or parotid metastasis. Objective To review our experience with parotidectomy in the treatment of these tumors to examine the indications for this procedure and to analyze treatment outcomes. We emphasize the importance of early identification of an ANMSC and a systematic approach to treatment. Design Review of 23 patients with an ANMSC who required parotidectomy with or without facial (VII) nerve sacrifice between January 5, 1996, and December 27, 1999. Median follow-up for all patients was 24 months. Setting Academic tertiary care referral center. Patients This study focused on 23 (median age, 71 years) of 54 patients treated for an ANMSC. Most tumors were in the periauricular (n = 9) and the frontozygomatic (n = 6) areas. Seven patients presented with facial weakness or paralysis. Three patients had clinically evident parotid metastasis, while 14 patients had tumors directly invading the parotid gland. Eighteen patients had recurrent disease that had been treated previously with Mohs micrographic surgery. Interventions Following wide local excision of the ANMSC, 12 patients had resection of the lateral parotid lobe with preservation of the nerve, while 11 required radical parotidectomy with sacrifice of 1 or more branches. Nineteen patients received cervical lymphadenectomy. Postoperative radiotherapy was administered in 19 patients. Main Outcome Measures Tumor pathologic findings (specifically, perineural invasion of the facial nerve), locoregional control or recurrence, disease-free survival, disease-specific survival, and overall survival. Results Neurotropic spread to the facial nerve was present in 6 patients and was more likely to occur in younger patients (51 vs 75 years, P = .006). Locoregional failures occurred in 9 patients following treatment. Patients who required parotidectomy in their surgical treatment for an ANMSC were more likely to have recurrent disease ( P = .0002). Disease-specific and overall survival was 79% and 69%, respectively, at 42 months. Conclusions Patients with ANMSC may require parotidectomy in the context of neurotropic spread, regional metastasis, or direct invasion into the parotid gland. Surgery combined with postoperative radiotherapy is necessary in most patients because of adverse clinical and pathologic findings. A systematic approach to the management of the parotid and facial nerve in the presence of these aggressive tumors is required. Despite comprehensive treatment, local recurrence of ANMSC and mortality remain high.

Objective To prove the efficacy of bone morphogenic protein as an osteoinductive agent in irradiated tissue. Design Prospective randomized controlled trial designed to test the effectiveness of recombinant bone morphogenic protein 2 (rBMP-2) combined with solid hydroxyapatite disks in an irradiated tissue bed. Subjects Eighteen adult, male, white New Zealand rabbits weighing 3.0 to 3.5 kg. Intervention The rabbits were randomly divided, with 9 receiving radiation treatment and 9 receiving no radiation treatment. Each animal underwent implantation of 2 hydroxyapatite disks onto the snout at 9 weeks following radiation treatment. One disk was impregnated with rBMP-2 and the other with buffer only. The animals were killed at 3, 6, or 20 weeks after implantation for analysis. Results Histological analysis demonstrated that rBMP-2 was equally effective as an osteoinductive agent in the irradiated and nonirradiated tissue. We also found significantly increased new bone formation in the rBMP-2 group vs the buffer group. Conclusions This study supports the potential clinical utility of rBMP-2 and solid hydroxyapatite in irradiated tissue beds. These findings have interesting implications for patients with head and neck cancer who have undergone radiation therapy and need bony reconstruction.