Surgical salvage improves overall survival for patients with HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer.

BACKGROUND: Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for patients with distant metastatic disease are limited. METHODS: A retrospective analysis of patients with recurrent OPSCC from 2 institutions between 2000 and 2012 was performed. p16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival (OS) was examined using Kaplan-Meier and Cox proportional hazards methods. RESULTS: The current study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority of patients were HPV-positive (80 patients). HPV-positive tumor status was associated with longer time to disease recurrence (P<.01). Anatomic site distribution of disease recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR], 0.23; 95% confidence interval [95% CI], 0.09-0.58 [P = .002]), longer time to disease recurrence (≥ 1 year; aHR, 0.36; 95% CI, 0.18-0.74 [P = .006]), and surgical salvage (aHR, 0.26; 95% CI, 0.12-0.61 [P = .002]) were found to be independently associated with OS after disease recurrence. Surgical salvage was independently associated with improved OS compared with nonsurgical treatment among patients with both locoregional (aHR, 0.15; 95% CI, 0.04-0.56 [P = .005]) and distant (aHR, 0.19; 95% CI, 0.05-0.75 [P = .018]) metastatic disease recurrences. CONCLUSIONS: Surgical salvage was found to be associated with improved OS for patients with recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data are needed to confirm the role of surgical salvage for distant metastases.

Pharyngocutaneous fistula after total laryngectomy: a single-institution experience, 2001-2012.

PURPOSE: The purpose of this study was to determine the incidence of and risk factors for pharyngocutaneous fistula in patients undergoing total laryngectomy at a single institution. MATERIALS AND METHODS: The records of 59 patients undergoing primary or salvage total laryngectomy at our institution from 2001 to 2012 were retrospectively reviewed. Data collected included patient, tumor and treatment characteristics, and surgical technique. Risk factors were analyzed for association with pharyngocutaneous fistula formation. RESULTS: Twenty patients (34%) developed fistulas. Preoperative tracheostomy (OR 4.1; 95% CI 1.3-13 [p=0.02]) and low postoperative hemoglobin (OR 9.1; 95% CI 1.1-78 [p=0.04]) were associated with fistula development. Regarding surgical technique, primary sutured closure of the total laryngectomy defect had the lowest fistula rate (11%). In comparison, primary stapled closure and pectoralis onlay flap over primary closure had nonsignificantly increased fistula rates (43%, OR 6.0; 95% CI 1.0-37.3 [p=0.06] and 25%, OR 2.7; 95% CI 0.4-23.9 [p=0.38], respectively). Pectoralis flap incorporated into the suture line had a significantly increased fistula rate (50%, OR 7.1; 95% CI 1.4-46 [p=0.02]). After stratification for salvage status, patient comorbidities were associated with fistula in non-salvage cases whereas disease-related characteristics were associated with fistula in salvage cases. Fistula development was associated with increased length of hospital stay (p<0.001) and increased time before oral diet initiation (p<0.001). CONCLUSIONS: Pharyngocutaneous fistula is a common complication of total laryngectomy. Preoperative tracheostomy, postoperative hemoglobin, and surgical technique are important in determining the risk of fistula.

Comparison of acute toxicities in two primary chemoradiation regimens in the treatment of advanced head and neck squamous cell carcinoma.

PURPOSE: The optimal dosage and frequency of platinum-based chemoradiotherapy (CRT) regimen for treating advanced head and neck squamous cell carcinoma remains unresolved. This study aims to compare the toxicity and efficacy of weekly versus more dose-intensive cisplatin-based CRTs. METHODS: We reviewed 155 stage III/IV head and neck squamous cell carcinoma patients with no evidence of distant metastasis treated with one of two CRT regimens from 2000 to 2010 at Greater Baltimore Medical Center. Twice-daily radiation was provided as a split course over a 45-day period. Regimen A consisted of concomitant cisplatin (30 mg/m2/1 h) weekly for 6 cycles; regimen B consisted of concomitant cisplatin (12 mg/m2/1 h) and 5-fluorouracil (600 mg/m2/20 h) on days 1 through 5 and days 29 through 33. Main outcome measures included acute toxicities (myelosuppression, neurotoxicity, nephrotoxicity, gastrointestinal dysfunction), unplanned hospitalizations, and disease control at 12 months. RESULTS: Patients on regimen A were much less likely to experience ototoxicity due to their treatment (0% vs. 9.8%, P = 0.04). They were more likely to experience thrombocytopenia acutely (46% vs. 26%, P = 0.02), but the toxicity was not limiting (grade 1­2). No significant differences exist in the incidence of other toxicities or unplanned hospitalizations. At 1 year, 97% of patients on A vs. 86% of patients on regimen B were free of disease (P = 0.11). CONCLUSIONS: With concurrent radiotherapy, low-dose, single-agent, weekly cisplatin is less likely than higher-dose daily cisplatin plus 5-fluorouracil provided at the beginning and end of treatment to be associated with ototoxicity. The preliminary data suggest at least equivalent efficacy, but longer follow-up is required.

Intraoperative Radiographic Assessment of Bone Resection Margins During Mandibulectomy: A Case Series.

BACKGROUND AND PURPOSE: Mandibulectomy remains the treatment of choice for oral cavity squamous cell carcinoma with infiltration of bone and for benign tumors with full mandibular thickness involvement. Although bone resection margins are critical for patient outcomes, intraoperative immediate bone margins assessment is inadequate, and few alternative options have been described. The purpose of this study was to describe the use of an existing intraoperative radiographic system for objective determination of bone resection margins during mandibulectomy. METHODS: We conducted a retrospective case series of all patients at the Greater Baltimore Medical Center who underwent mandibulectomy and received intraoperative Faxitron radiography from January 1, 2016, to March 1, 2019. Patient characteristics including age, sex, diagnosis, tumor location, clinical and pathologic stage, procedure performed, and bone resection margins were reviewed. RESULTS: A total of 10 patients underwent mandibulectomy with intraoperative radiography. Nine (90%) received surgery for squamous cell carcinoma, with 1 (10%) for ameloblastoma. Out of those with squamous cell carcinoma, tumor location varied, and all were clinically stage T4. Final pathologic margins were negative in all cases (10/10), though in 2 cases, close margins were assessed intraoperatively, leading to further resection or change in operative plan. CONCLUSION: Intraoperative radiographic assessment of bone resection margins is a promising technique, though further validation is required.

Reader performance in the ultrasonographic evaluation of oropharyngeal carcinoma.

OBJECTIVE: To examine reader performance in evaluating oropharyngeal anatomy on ultrasonography. MATERIALS AND METHODS: Ultrasound images of the oropharynx comprising normal and malignant anatomic variants were organized into slideshows. Slideshows were administered to 6 readers blinded to participant tumor status and with varying experience reading oropharyngeal sonograms. A training slideshow oriented readers to images of the oropharynx with and without malignant lesions. Readers then evaluated images in a test slideshow for tumor presence and marked orthogonal long and short dimensions of the tumor. Results were analyzed for accuracy, sensitivity, specificity, inter-reader agreement, and measurement error relative to prospectively-identified reference measurements. RESULTS: Eighty-seven percent of base of tongue (BOT) sonograms were identified correctly by a majority of readers. In identifying BOT tumors, median accuracy, sensitivity, specificity, and Fleiss's kappa were 79%, 73%, 85%, and 0.51, respectively. Median measurement error in the long and short axes for BOT tumors was -2.6% (range: -40% to 29%) and -2.6% (range: -56% to 156%), respectively. Eighty-four percent of palatine tonsil sonograms were identified correctly by a majority of readers. In identifying tonsil tumors, median accuracy, sensitivity, specificity, and Fleiss's kappa were 77%, 74%, 78%, and 0.41, respectively. Median measurement error in the long and short axes for tonsil tumors was 3.8% (range: -45% to 32%) and -6.5% (range: -83% to 42%), respectively. CONCLUSIONS: Overall, US has clinically useful sensitivity for identification of oropharyngeal carcinoma among readers of diverse clinical backgrounds and experience. US may be useful for the evaluation of features such as tumor dimensions.

Abdominal wall endometriomas.

BACKGROUND: The diagnosis of abdominal wall endometriomas is often confused with other surgical conditions. METHODS: A retrospective study was made of 12 patients presenting with an abdominal wall mass, which proved to be endometrioma. RESULTS: Of a total of 297 patients of endometriosis treated in our hospital over a 7-year period, 12 (4%) had isolated abdominal wall endometriomas. Their mean age was 29.4 years. The presenting symptoms were abdominal mass (n = 12), cyclical (n = 5) or noncyclic pain (n = 7), dyspareunia and dysmenorrhea (n = 1). All patients had a history of gynecologic operations and presented, after an average of 1.9 years, with a tender mass (average 4 cm) at the previous incision site. Preoperative diagnosis was correct in 4 patients (33%) who presented with a cyclically painful abdominal mass. The others were diagnosed as incisional hernia (n = 4), "abdominal wall tumor" (n = 2), and inguinal hernia (n = 2). All patients underwent wide excision of their endometrioma; 2 required polytetrafluoroethylene patch grafting for the resulting fascial defect. The diagnosis was confirmed at frozen section or conventional histological examination in all patients. At follow-up, ranging from 4 months to 3 years, there was no recurrence of endometrioma. CONCLUSIONS: Scar endometrioma commonly presents as an abdominal mass with noncyclical symptoms. Imaging techniques are nonspecific and needle biopsy may confirm the diagnosis. Wide excision is the treatment of choice for abdominal wall endometrioma as well as for recurrent lesions.

Transoral robotic surgery experience in 44 cases.

OBJECTIVE: To report a single institution's experience with transoral robotic surgery (TORS) and its clinical outcomes. This was a retrospective study carried out at a university-affiliated teaching hospital. SUBJECTS AND METHODS: Forty-four consecutive TORS patients with benign and malignant diseases were reviewed. Data on demographics, clinical parameters, and diet were collected. Surgical margins, local and regional recurrence, distant metastasis, 2-year disease-free survival rate, and 2-year survival data were reviewed for the malignant cases. RESULTS: Nine benign and 35 proven squamous cell carcinoma (SCCA) cases underwent TORS. The set-up time was 17.12 minutes (range, 10-40 minutes), and operative time was 53 minutes (range, 10-300 minutes). Average length of stay was 2.5 days. There were seven (6.8%) grade 3 surgical complications. Surgical infection rate was 2.3%. Benign cases were on a regular diet after TORS. Of the malignant cases, 94% were taking peroral diet immediately after the TORS procedure. There were no intraoperative complications and no 30-day postoperative mortalities. The mean follow-up time was 25.2 months (range, 16-38 months) for malignant disease. The SCCA sites were in the oropharynx (30/35), larynx (2/35), and unknown primary with neck metastasis (3/35). Unknown primary patients were excluded in the surgical margin analyses. Negative margins were achieved in 91% of cases. The local and regional recurrence rates were 6.3% (2/32) and 3.1% (1/32), respectively. Two patients (6.3%) developed distant metastasis. Oropharyngeal SCCA cases were reviewed, of which 23 were human papillomavirus (HPV)/p16 positive and 7 were HPV/p16 negative. The 2-year actual survival for HPV-positive and -negative patients was 96% (22/23) and 86% (6/7), respectively. The 2-year disease-free survival for HPV-positive and -negative cases was 91% (21/23) and 71.4% (5/7), respectively. All malignant cases that underwent TORS received postoperative adjuvant therapy. CONCLUSIONS: TORS is a safe procedure with minimal complications and acceptable clinical and functional outcomes.

Neck dissection through a facelift incision.

OBJECTIVES/HYPOTHESIS: To determine the feasibility and safety of neck dissection through a facelift incision. STUDY DESIGN: Prospective case series. METHODS: Cadavers and live subjects underwent neck dissection using a facelift incision with and without endoscopic assistance. In the live facelift neck dissection (FLND), the preoperative surgical indications, staging, adjuvant therapy, intraoperative technical procedure, pathology reports on lymph nodes, and short-term outcomes were reviewed. RESULTS: FLND was successfully performed in four cadavers and four live subjects, including selective (less than five neck levels removed) and comprehensive (levels I-V removed) neck dissections. All levels were accessible through this approach, with additional retraction required for levels I and IV. Endoscopic assistance was required in one neck dissection for adequate visualization. Short-term complications and number of excised lymph nodes were comparable to those from traditional neck dissection approaches. CONCLUSIONS: Open neck dissection through a facelift incision is feasible and offers an alternate approach to traditional incisions. This can be performed without requiring robotic assistance and with endoscopic assistance only in certain cases. Endoscopic assistance can offer enhanced visualization of the surgical field and complement open direct approaches in neck dissection. Although FLND offers improved cosmetic outcomes when compared to those of traditional neck incisions, further study is required to determine its efficacy and indications.

The effect of amifostine on submandibular gland histology after radiation.

Background. The purpose of this study was to assess the effects of amifostine on submandibular gland histology in patients receiving chemoradiation therapy. Methods. We conducted a retrospective submandibular gland histologic slide review of HNSCC patients receiving chemoradiation for head and neck squamous cell carcinoma with three different levels of amifostine exposure. We used six scoring parameters: fatty replacement, lobular architecture degeneration, interstitial fibrosis, ductal degeneration, acinar degeneration, and inflammatory component presence. Results. Differences in gender, tumor stage, amifostine dose, age, number of days after neck dissection, and smoking history (pack years) exposure were not significant between the three groups, although there was a difference between groups in the primary subsite (P = 0.006). The nonparametric Cuzick's test for histologic parameters with varied amifostine treatment showed no significance among the three groups. Conclusions. Although patients did not receive a full dose of amifostine due to side effects, varying doses of amifostine had no apparent evident cytoprotective effects in three groups of cancer patients treated with primary chemoradiation.

Multidisciplinary service utilization pattern by advanced head and neck cancer patients: a single institution study.

Purpose. To analyze the patterns and associations of adjunctive service visits by head and neck cancer patients receiving primary, concurrent chemoradiation therapy. Methods. Retrospective chart review of patients receiving adjunctive support during a uniform chemoradiation regimen for stages III-IV head and neck squamous cell carcinoma. Univariate and multivariate models for each outcome were obtained from simple and multivariate linear regression analyses. Results. Fifty-two consecutive patients were assessed. Female gender, single marital status, and nonprivate insurance were factors associated with an increased number of social work visits. In a multivariate analysis, female gender and marital status were related to increased social work services. Female gender and stage IV disease were significant for increased nursing visits. In a multivariate analysis for nursing visits, living greater than 20 miles between home and hospital was a negative predictive factor. Conclusion. Treatment of advanced stage head and neck cancer with concurrent chemoradiation warrants a multidisciplinary approach. Female gender, single marital status, and stage IV disease were correlated with increased utilization of social work and nursing services. Distance over 20 miles from the center was a negative factor. This information may help guide the treatment team to allocate resources for the comprehensive care of patients.

Hyperfractionated radiotherapy with concurrent cisplatin/5-Fluorouracil for locoregional advanced head and neck cancer: analysis of 105 consecutive patients.

Objective. We reviewed a cohort of patients with previously untreated locoregional advanced head and neck squamous cell carcinoma (HNSCC) who received a uniform chemoradiotherapy regimen. Methods. Retrospective review was performed of 105 patients with stage III or IV HNSCC treated at Greater Baltimore Medical Center from 2000 to 2007. Radiation included 125 cGy twice daily for a total 70 Gy to the primary site. Chemotherapy consisted of cisplatin (12 mg/m(2)/h) daily for five days and 5-fluorouracil (600 mg/m(2)/20 h) daily for five days, given with weeks one and six of radiation. All but seven patients with N2 or greater disease received planned neck dissection after chemoradiotherapy. Primary outcomes were overall survival (OS), locoregional control (LRC), and disease-free survival (DFS). Results. Median followup of surviving patients was 57.6 months. Five-year OS was 60%, LRC was 68%, and DFS was 56%. Predictors of increased mortality included age ≥55, female gender, hypopharyngeal primary, and T3/T4 stage. Twelve patients developed locoregional recurrences, and 16 patients developed distant metastases. Eighteen second primary malignancies were diagnosed in 17 patients. Conclusions. The CRT regimen resulted in favorable outcomes. However, locoregional and distant recurrences cause significant mortality and highlight the need for more effective therapies to prevent and manage these events.

Factors associated with pharyngoesophageal stricture in patients treated with concurrent chemotherapy and radiation therapy for oropharyngeal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to elucidate factors associated with pharyngoesophageal strictures after treatment for head and neck squamous cell carcinoma (SCC). METHODS: We conducted a retrospective review of patients receiving cisplatin and 5-fluorouracil chemotherapy combined with concurrent hyperfractionated radiation therapy for oropharyngeal squamous cell carcinoma. RESULTS: Strictures developed in 13 of 67 patients (19%). Strictures were associated with tumor location (tonsil vs base of tongue; p = .03), neck dissection after completion of therapy (p = .03), and the duration of treatment-induced mucositis (weeks with mucositis grade ≥2; National Cancer Institute (NCI) Common Toxicity Criteria; p < .001). Age, sex, race, tumor stage, nodal stage, American Joint Committee on Cancer (AJCC) stage, human papillomavirus (HPV) status, smoking, radiation dose, maximum severity of mucositis, amifostine use, and pretreatment swallow dysfunction were not significantly associated with stricture. In multivariate analysis, only duration of mucositis, after controlling for age, sex, and tumor location, remained highly significant (p < .01). CONCLUSION: The duration of treatment-related mucositis is an independent risk factor for stricture formation in patients with oropharyngeal SCC treated with concurrent chemotherapy and radiation therapy.

Selective versus comprehensive neck dissection after chemoradiation for advanced oropharyngeal squamous cell carcinoma.

OBJECTIVE: To determine whether a comprehensive neck dissection (CND) or a selective neck dissection (SND) is indicated as planned post-primary chemoradiation treatment (CRT) for patients with advanced oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Case series with chart review. SETTING: A community teaching hospital. SUBJECTS: Patients with advanced OPSCC who received a uniform CRT protocol at Greater Baltimore Medical Center (GBMC). METHODS: Medical records of patients treated with primary CRT for locoregionally advanced OPSCC at GBMC between 2001 and 2007 were reviewed. All patients received 7000 to 7500, 6000, and 5000 cGy to primary disease sites, involved cervical lymphatics, and uninvolved cervical and supraclavicular lymphatics, respectively, with concomitant cisplatin (12 mg/m(2)/1 h) and 5-fluorouracil (600 mg/m(2)/20 h) given on days one through five and 29 through 33. RESULTS: Seventy-six patients received CRT, and 41 met the criteria for neck dissection. Forty-eight neck dissections were performed (34 unilateral and 7 bilateral), of which 23 (48%) were CNDs and 25 (52%) were SNDs. Residual carcinoma was found in six (26%) of the CND and five (20%) of the SND heminecks. The CND group had six (26%) complications, whereas the SND group had two (8%). CONCLUSION: The high rate of residual disease demonstrated in this study supports the need for post-CRT neck dissection. Although complication rates were not significantly different between the two groups, the trend in this study indicates that SND results in less morbidity. The presumed reduced morbidity and equivalent regional control rate suggest that SND is an appropriate surgical option for OPSCC patients after primary CRT.