Citations

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.

ObjectiveOptimal timing of postoperative radiotherapy (PORT) remains understudied in human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma. Objectives are to determine if delays between surgery and radiotherapy, breaks during radiotherapy, disease, or patient factors are associated with recurrence or survival decrements in HPV‐related disease.DesignRetrospective review.SettingAcademic medical center.SubjectsA total of 240 cases of HPV‐positive oropharyngeal squamous cell carcinoma from 2000 to 2016.MethodsPatient and tumor characteristics (American Joint Committee on Cancer, eighth edition), delays to radiation initiation, and breaks during radiation were recorded. Overall survival (OS) and recurrence‐free survival (RFS) were analyzed.ResultsRFS and OS were not significantly affected by delays to PORT >6 weeks or by treatment intervals >100 days (surgery to PORT completion). Breaks during PORT significantly imparted an OS detriment (hazard ratio [HR], 2.4; 95% CI, 1.2‐4.8). Advanced‐stage disease was significantly associated with reduced RFS and OS. Subgroup analysis of stage I versus stage II/III disease found that >6 weeks to PORT initiation and treatment intervals >100 days did not significantly decrease RFS or OS in either stage group. Advanced‐stage disease was significantly associated with worsened OS (HR, 6.6; 95% CI, 2.3‐19.1) and RFS (HR, 5.3; 95% CI, 1.5‐18.4). Breaks during PORT significantly reduced RFS (HR, 3.6; 95% CI, 1.2‐10.8) and OS (HR, 3.2; 95% CI, 1.2‐9.0) in the stage II/III subset.ConclusionDelays to radiotherapy initiation and prolonged treatment time did not affect recurrence or survival in HPV‐related oropharyngeal disease. Locoregionally advanced disease was consistently associated with worse outcomes. Breaks during PORT may affect recurrence and survival, although larger studies are needed to confirm this finding.

Importance The clinical and financial implications of the timing of dental rehabilitation after a fibula free tissue transfer (FFTT) for osteoradionecrosis (ORN) and osteonecrosis (ON) of the mandible have yet to be established. Objective To compare the outcomes of primary implantation vs secondary implantation after FFTT for ORN and ON of the mandible. Design, Setting, and Participants A retrospective review was conducted of 23 patients at a single tertiary academic referral center undergoing primary implantation or secondary implantation after FFTT for ORN and ON from January 1, 2006, to November 10, 2015. Interventions All patients underwent FFTT with primary implantation (n = 12) or secondary implantation (n = 11). Main Outcomes and Measures Outcomes of FFTT, dental implantation, implant use, diet, speech, and disease-free survival were reviewed. Fixed unit costs were estimated based on the mean cost analysis. Results Twenty-three patients (7 women and 16 men; mean [SD] age, 62.4 [8.2] years [range, 24-81 years]) met the inclusion criteria. Of these, 18 had ORN and 5 had ON. Dental implantation was performed at the time of FFTT for 12 patients and was performed secondarily for 11 patients. There were a mean of 5.2 implants per patient performed, for a total of 121 implants. There was 1 complete flap failure in the primary implantation group. Neither flap nor implant complications were affected by the timing of the implantation. Overall, the implant survival rate was 95% (55 of 58) in the primary implantation group and 98% (62 of 63) in the secondary implantation group. Time from FFTT to abutment placement (primary implantation, 19.6 weeks; secondary implantation, 61.0 weeks) was significantly shorter after primary implantation ( P < .001). There was no clinical difference in postoperative complications and implant outcomes for ORN vs ON. Improvement in speech and oral competence in the primary implantation group vs the secondary implantation group was not statistically significant, given an experiment-adjusted P = .001 set as significant (normal speech, 9 vs 3; P = .02; and normal oral competence, 9 vs 3; P = .02). Disease-free survival was 91% (20 of 22 patients) overall. Fixed unit (U) costs were 1.0 U for primary implantation and 1.24 U for secondary implantation. Conclusions and Relevance Patients undergoing primary implantation after FFTT for ORN and ON had a similar rate of complications compared with those undergoing secondary implantation. However, primary implantation allowed a faster return than secondary implantation to oral nutrition and prosthesis use. The fixed unit cost was reduced for those undergoing primary implantation. Although dental implantation was safe and effective in both groups, the decreased time to use and the decreased overall cost should prompt surgeons to consider primary implantation after FFTT for ORN and ON. Level of Evidence 3 .

AbstractBackgroundOncologic outcomes of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (SCC) requiring resection of major muscular or neurovascular tissue during neck dissection for invasive nodal disease remain uncertain.MethodsPatients with HPV‐related oropharyngeal SCC requiring resection of major muscular or neurovascular tissue during their neck dissections were retrospectively identified.ResultsSeventy‐two patients were included. Regional and distant recurrences occurred in 6% and 17% of patients. Advanced T classification, pathological node number of 5 or more, and omission of adjuvant therapy were associated with decreased disease‐free survival (DFS). The addition of adjuvant chemotherapy was not associated with improved survival.ConclusionPatients with invasive nodal disease from HPV‐related oropharyngeal SCC can be managed with up‐front surgery and adjuvant therapy, as indicated with good regional control. Although distant recurrence was the primary site of failure, adjuvant chemotherapy was not associated with improved outcomes. The T classification, node number, and adjuvant radiotherapy are independent prognostic factors in this patient population.

AbstractBackgroundThis study presents oncologic outcomes after transoral robotic surgery (TORS) ± adjuvant therapy for oropharyngeal squamous cell carcinoma (SCC).MethodsThree hundred fourteen patients undergoing TORS ± adjuvant therapy for oropharyngeal SCC from May 1, 2007, to May 31, 2015, are analyzed.ResultsMedian follow‐up was 3.3 years (interquartile range [IQR] 1.8‐5.3 years; range 1 day to 9.3 years). Estimated locoregional recurrence‐free survival, distant metastasis‐free survival (DMFS), overall survival (OS), and cancer‐specific survival (CSS) rates (95% confidence interval [CI] number still at risk) at 5 years after surgery were 92% (88‐95; 92), 90% (86‐94; 92), 86% (82‐92; 98), and 94% (91‐97; 98), respectively. Negative margins were achieved in 98% of cases. The adult comorbidity evaluation (ACE)‐27 comorbidity index, human papillomavirus (HPV) status, pathologic N classification, and number of attempts to clear margins were associated with death due to cancer (P = .003, P = .002, P = .030, and P = .002, respectively).ConclusionThe need to take ≥2 margins to achieve resection portends an increased risk of locoregional recurrence and death due to disease in oropharyngeal SCC.

ObjectiveHuman adipose‐derived mesenchymal stem cells (ADSCs) were used to rehabilitate bone damaged by osteoradionecrosis (ORN) in an established animal model.Study DesignProspective animal study.SettingAcademic department laboratory.Subjects and MethodsAfter institutional review board and Institutional Animal Care and Use Committee approval, 24 athymic nude rats were divided into 5 groups: 4 groups irradiated (20 Gy) by brachytherapy catheter placed at the left hemimandible and 1 mock irradiation control (n = 4). For all groups, ORN was initiated by extraction of the central molar 1 week later. After 28 days, animals (n = 5/group) received injection at the extraction site with saline (SAL), ADSCs, platelet‐rich plasma and collagen (PRP/COL), or ADSCs + PRP/COL. Rats were sacrificed 28 days later and their mandibles harvested for histopathology analysis (osteoblasts, osteoclasts, and fibrosis) and bone volume measurement using 3‐dimensional micro–computed tomography.ResultsAll but 1 rat survived the experiment period (23/24). Radiographic and histological analysis revealed 60% bone loss in the SAL group compared with the nonirradiated control. Injection of ADSCs increased jaw region bone volume by up to 36% (P <. 01). All experimental groups (ADSC, PRP/COL, and ADSC + PRP/COL) showed dramatically decreased osteoclast counts (P <. 001) while injection of PRP/COL with or without ADSCs increased osteoblasts. Increased fibrosis was observed after ADSC injection (P <. 05).ConclusionThe application of human ADSCs to an induced mandibular osteoradionecrosis model in athymic rats results in increased deposition or preservation of bone, demonstrated both histologically and radiographically. This offers an encouraging possible treatment option for translational research in this difficult disease.

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

Objective: To report hemifacial spasm (HFS) as a rare presenting symptom of a benign parotid neoplasm involving the stylomastoid foramen. Methods: Case report with literature review. Results: An 18-year-old woman presented with a 1-year history of a progressively enlarging right infra-auricular mass with new onset ipsilateral severe HFS. Clinical vetting unveiled a palpable 2 cm, firm, minimally mobile mass medial to the angle of the mandible. Imaging revealed a heterogeneous intraparotid mass with tumor extension into the stylomastoid foramen. Diagnostic consideration was given to neurogenic tumors and neoplasms of parotid origin. The patient ultimately underwent superficial parotidectomy and the tumor was found superficial and extrinsic to the proximal facial nerve trunk but extended into the stylomastoid foramen. The tumor was removed after performing mastoidectomy with mastoid segment facial nerve decompression. Frozen section pathology was consistent with pleomorphic adenoma. Postoperatively the patient had normal facial nerve function with immediate and complete resolution of HFS. To date there are only three other published reports of benign parotid tumors presenting with HFS and this is the first illustrating intratemporal tumor extension. Conclusions: HFS is a rare presenting symptom associated with benign parotid neoplasms with scarce documentation in the literature. In this index case, tumor extirpation with mastoid segment facial nerve decompression provided immediate and durable resolution of symptoms.

ObjectivesTo examine outcomes of selective neck dissection (SND) in patients with human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (OPSCC) who present with clinical neck disease.Study DesignMulti‐institutional retrospective review.MethodsTwo institutional databases of patients with HPV‐related OPSCC were reviewed to identify patients with clinical (c) N1‐N3 neck disease who underwent SND ± adjuvant therapy.ResultsThree hundred and twenty‐four patients were identified with a median follow‐up of 49 months (range 3–199 months). All patients underwent transoral resection of the primary tumor and SND, including levels II–IV and ± levels I or V, with resection of additional nonlymphatic tissue (extended SND) as indicated by extent of disease, including the spinal accessory nerve (7%), the internal jugular vein (13%), and the sternocleidomastoid muscle (8%). Two hundred and seventy (83%) patients underwent adjuvant radiation. There were 13 (4%) regional recurrences and 19 (6%) distant recurrences. Regional control following salvage was 98%. On univariable analysis, absence of radiation was associated with regional recurrence (odds ratio [OR] 9.2, 95% confidence interval [CI] 2.9–29.4). On multivariable analysis, adjuvant radiation was associated with improved disease‐free survival (DFS) (OR 0.27, 95% CI 0.14–0.53) but lost significance for overall (OS) and disease‐specific survival (DSS) (P > 0.05). Five‐year Kaplan‐Meier estimates for OS, DSS, and DFS were 88% (95% CI 84%–92%), 93% (95% CI 89%–96%), and 83% (95% CI 78%–87%), respectively.ConclusionIn HPV‐related OPSCC presenting with clinical neck disease, a SND ± additional tissue resection and adjuvant therapy, when indicated, provides excellent long‐term regional control. Omission of radiotherapy increases the risk of regional recurrence, although it may not significantly impact OS or DSS. It appears unnecessary to routinely perform a comprehensive neck dissection.Level of Evidence4. Laryngoscope, 127:623–630, 2017