Postoperative adjuvant therapy after transoral robotic resection for oropharyngeal carcinomas: rationale and current treatment approach.

The advancement of transoral surgical techniques for the management of oropharyngeal carcinomas has raised questions about how adjuvant therapy can best be integrated. Some of these questions have come from the application of established oncologic principles of adjuvant therapy, and some are unique to the evolving experience with transoral surgery and in particular with the recent advancement of robotic surgery. It is important for all members of the multidisciplinary treatment team to have a clear understanding of the foundation for adjuvant therapy and the issues unique to transoral robotic surgery to provide optimal patient care as this new treatment paradigm gains popularity for its safe application.

Lesion oxygenation associates with clinical outcomes in premalignant and early stage head and neck tumors treated on a phase 1 trial of photodynamic therapy.

BACKGROUND: We report on a Phase 1 trial of photodynamic therapy (PDT) for superficial head and neck (H&N) lesions. Due to known oxygen dependencies of PDT, translational measurements of lesion hemoglobin oxygen saturation (StO2) and blood volume (tHb) were studied for associations with patient outcomes. METHODS: PDT with aminolevulinc acid (ALA) and escalating light doses was evaluated for high-grade dysplasia, carcinoma-in-situ, and microinvasive carcinomas of the H&N. Among 29 evaluable patients, most (18) had lesions of the tongue or floor of mouth (FOM). Disease was intact in 18 patients and present at surgical margins in 11 patients. In 26 patients, lesion StO2 and tHb was measured. RESULTS: Local control (LC) at 24 months was 57.5% among all patients. In patients with tongue/FOM lesions LC was 42.7%, and it was 50.1% for those with intact lesions. Lesion tHb was not associated with 3-month complete response (CR), but StO2 was higher in patients with CR. In tongue/FOM lesions, baseline StO2 [mean(SE)] was 54(4)% in patients (n=12) with CR versus 23(8)% in patients (n=6) with local recurrence/persistence (p=0.01). Similarly, for intact disease, baseline StO2 was 54(3)% in patients (n=10) with CR versus 28(8)% in patients (n=5) without CR (p=0.03). In patients with intact disease, higher baseline StO2 associated with 24-month local control (p=0.02). CONCLUSIONS: Measurement of the physiologic properties of target lesions may allow for identification of patients with the highest probability of benefiting from PDT. This provides opportunity for optimizing light delivery based on lesion characteristics and/or informing ongoing clinical decision-making in patients who would most benefit from PDT.

A data-mining framework for large scale analysis of dose-outcome relationships in a database of irradiated head and neck cancer patients.

PURPOSE: To develop a hypothesis-generating framework for automatic extraction of dose-outcome relationships from an in-house, analytic oncology database. METHODS: Dose-volume histograms (DVH) and clinical outcomes have been routinely stored to the authors' database for 684 head and neck cancer patients treated from 2007 to 2014. Database queries were developed to extract outcomes that had been assessed for at least 100 patients, as well as DVH curves for organs-at-risk (OAR) that were contoured for at least 100 patients. DVH curves for paired OAR (e.g., left and right parotids) were automatically combined and included as additional structures for analysis. For each OAR-outcome combination, only patients with both OAR and outcome records were analyzed. DVH dose points, DVt, at a given normalized volume threshold Vt were stratified into two groups based on severity of toxicity outcomes after treatment completion. The probability of an outcome was modeled at each Vt = [0%, 1%, …, 100%] by logistic regression. Notable OAR-outcome combinations were defined as having statistically significant regression parameters (p < 0.05) and an odds ratio of at least 1.05 (5% increase in odds per Gy). RESULTS: A total of 57 individual and combined structures and 97 outcomes were queried from the database. Of all possible OAR-outcome combinations, 17% resulted in significant logistic regression fits (p < 0.05) having an odds ratio of at least 1.05. Further manual inspection revealed a number of reasonable models based on either reported literature or proximity between neighboring OARs. The data-mining algorithm confirmed the following well-known OAR-dose/outcome relationships: dysphagia/larynx, voice changes/larynx, esophagitis/esophagus, xerostomia/parotid glands, and mucositis/oral mucosa. Several surrogate relationships, defined as OAR not directly attributed to an outcome, were also observed, including esophagitis/larynx, mucositis/mandible, and xerostomia/mandible. CONCLUSIONS: Prospective collection of clinical data has enabled large-scale analysis of dose-outcome relationships. The current data-mining framework revealed both known and novel dosimetric and clinical relationships, underscoring the potential utility of this analytic approach in hypothesis generation. Multivariate models and advanced, 3D dosimetric features may be necessary to further evaluate the complex relationship between neighboring OAR and observed outcomes.

Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas.

To explore the potential of tumor-specific DNA as a biomarker for head and neck squamous cell carcinomas (HNSCC), we queried DNA from saliva or plasma of 93 HNSCC patients. We searched for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n = 10) and 95% (n = 37), respectively. When segregated by site, tumor DNA was detected in 100% (n = 15), 91% (n = 22), 100% (n = 7), and 100% (n = 3) of patients with tumors of the oral cavity, oropharynx, larynx, and hypopharynx, respectively. In saliva, tumor DNA was found in 100% of patients with oral cavity cancers and in 47 to 70% of patients with cancers of the other sites. In plasma, tumor DNA was found in 80% of patients with oral cavity cancers, and in 86 to 100% of patients with cancers of the other sites. Thus, saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in saliva was found postsurgically in three patients before clinical diagnosis of recurrence, but in none of the five patients without recurrence. Tumor DNA in the saliva and plasma appears to be a potentially valuable biomarker for detection of HNSCC.

Feasibility of rapid discharge after transoral robotic surgery of the oropharynx.

OBJECTIVES/HYPOTHESIS: To investigate the use of an algorithm for rapid discharge after transoral robotic surgery (TORS) and its effect on postoperative complications. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective analysis of TORS cases from September 2009 to February 2013 was conducted. The effect of patient and tumor characteristics on postoperative length of stay (LOS) and complications were analyzed. RESULTS: A total of 91 patients were included; 79 underwent TORS for malignancy and 12 for a benign process. The mean LOS was 1.51 days (range, 1-5 days) with a median of 1 day. The mean time to initiation of oral diet was 1.26 days (range, 1-7 days) with a median of 1 day. Eleven (12%) patients experienced one or more complications during their postoperative course. Multivariate analysis demonstrated a significant association between patient and procedure variables and postoperative complications. TORS base of tongue reduction for obstructive sleep apnea (OSA) was associated with a significantly greater mean incremental time to initiation of oral diet (1.0 days, 95% confidence interval [CI]: 0.4 to 1.7, P < .001). A significantly greater mean incremental LOS was observed for patients with advanced comorbidity and a delay in initiation of oral diet beyond 24 hours. CONCLUSIONS: Rapid initiation of oral diet and rapid discharge home is feasible and not associated with postoperative complications. Similarly, the performance of a concurrent neck dissection does not contribute to LOS or the development of postoperative complications. Patients undergoing TORS for OSA are at greater risk of delay in initiation of oral diet and increased LOS. LEVEL OF EVIDENCE: 4

Radiation dose to the floor of mouth muscles predicts swallowing complications following chemoradiation in oropharyngeal squamous cell carcinoma.

OBJECTIVES: While radiation dose to the larynx and pharyngeal constrictors has been the focus of swallowing complications, the suprahyoid muscles, or floor of mouth (FoM) muscles, are critical for hyoid and laryngeal elevation and effective bolus diversion, preventing penetration and aspiration. We hypothesize that radiation dose to these muscles may be important in the development of dysphagia. MATERIALS AND METHODS: We studied 46 patients with OPSCC treated with CRT and who underwent baseline swallowing evaluations and post-treatment videofluoroscopic swallowing studies (VFSS) from 2007 to 2010. Patients with abnormal penetration aspiration scores (PAS>2) served as the study population and patients with normal PAS scores (≤ 2) served as the control cohort. Three suprahyoid muscles and two extrinsic tongue muscles were individually delineated and collectively referred to as the FoM muscles. Radiation dose-volume relationships for these muscles were calculated. Univariate logistic regression analysis was used to determine parameters of significance between patients with normal or abnormal PAS scores. A multivariate regression analysis was subsequently performed to isolate the most statistically critical structures associated with abnormal PAS. RESULTS: Univariate analysis resulted in significance/borderline significance of multiple structures associated with abnormal PAS following irradiation. However, when a multivariate model was applied, only the mean dose to the floor of mouth and minimum dose to the geniohyoid were associated with post-radiation abnormal PAS. CONCLUSIONS: The dose and volume delivered to the collective FoM muscles may be associated with an increased risk of laryngeal penetration/aspiration to a greater degree than previously recognized organs at risk.

Transoral resection of pharyngeal cancer: summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia.

Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6-7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)-initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized.