Harry Quon

Diffusion-Weighted Magnetic Resonance Imaging for Predicting and Detecting Early Response to Chemoradiation Therapy of Squamous Cell Carcinomas of the Head and Neck

Purpose: The aim of this study was to investigate the utility of apparent diffusion coefficient (ADC) for prediction and early detection of treatment response in head and neck squamous cell carcinomas (HNSCC). Experimental Design: Diffusion-weighted magnetic resonance imaging studies were performed on 40 patients with newly diagnosed HNSCC before, during, and after the end of chemoradiation therapy. Analysis was done on data from 33 patients after exclusion of 7 patients that had incomplete data. Results: Pretreatment ADC value of complete responders (1.04 ± 0.19 × 10−3 mm2/s) was significantly lower (P < 0.05) than that from partial responders (1.35 ± 0.30 × 10−3 mm2/s). A significant increase in ADC was observed in complete responders within 1 week of treatment (P < 0.01), which remained high until the end of the treatment. The complete responders also showed significantly higher increase in ADC than the partial responders by the first week of chemoradiation (P < 0.01). When pretreatment ADC value was used for predicting treatment response, the area under the receiver operating characteristic curve was 0.80 with a sensitivity of 65% and a specificity of 86%. However, change in ADC within the first week of chemoradiation therapy resulted in an area under the receiver operating characteristic curve of 0.88 with 86% sensitivity and 83% specificity for prediction of treatment response. Conclusions: These results suggest that ADC can be used as a marker for prediction and early detection of response to concurrent chemoradiation therapy in HNSCC.

Transoral Robotic Surgery for Advanced Oropharyngeal Carcinoma

OBJECTIVES To determine the oncologic and functional outcomes in patients undergoing primary transoral robotic surgery followed by adjuvant therapy as indicated with a minimum of 18-month follow-up for advanced oropharyngeal carcinoma. DESIGN Prospective single-center cohort study. SETTING Academic university health system and tertiary referral center. PATIENTS Forty-seven adults with newly diagnosed and previously untreated advanced oropharyngeal carcinoma. INTERVENTION Transoral robotic surgery with staged neck dissection and adjuvant therapy as indicated. MAIN OUTCOME MEASURES Margin status, recurrence, disease-specific and disease-free survival, gastrostomy tube dependence, and safety and efficacy end points. RESULTS In the 47 patients enrolled with stages III and IV advanced oropharyngeal carcinoma, mean follow-up was 26.6 months. There was no intraoperative or postoperative mortality. Resection margins were positive in 1 patient (2%). At last follow-up, local recurrence was identified in 1 patient (2%), regional recurrence in 2 (4%), and distant recurrence in 4 (9%). Disease-specific survival was 98% (45 of 46 patients) at 1 year and 90% (27 of 30 patients) at 2 years. Based on pathologic risk stratification, 18 of 47 patients (38%) avoided chemotherapy, and 5 patients (11%) did not receive adjuvant radiotherapy and concurrent chemotherapy in their treatment regimen. At minimum follow-up of 1 year, only 1 patient required a gastrostomy tube. CONCLUSIONS This novel transoral robotic surgery treatment regimen offers disease control, survival, and safety commensurate with standard treatments and an unexpected beneficial outcome of gastrostomy dependency rates that are markedly lower than those reported with standard nonsurgical therapies.

Transoral robotic surgery and human papillomavirus status: Oncologic results

Patients with oropharyngeal squamous cell carcinoma (OPSCC) have been shown to have distinct outcome profiles based on their human papillomavirus (HPV) status. The purpose of this study was to assess HPV‐related outcomes after transoral robotic surgery (TORS) with adjuvant therapy as indicated.

Transoral robotic surgery: does the ends justify the means?

Purpose of reviewHead and neck surgical science has developed dramatically during the past 20 years with a major focus on organ preservation surgery. Among these organ preserving surgeries are the selective neck dissections, supracricoid partial laryngectomies, transoral laser surgeries, and now a newcomer, transoral robotic surgery utilizing the da Vinci surgical system. Transoral robotic surgery is in its infancy, but, indeed, there have been some questions raised about the role of these innovative robotic surgical techniques. Recent findingsThis article will review, point by point, the questions that have been raised concerning the feasibility; safety and efficacy; teachability; and cost effectiveness of transoral robotic surgery. SummaryAlthough the present literature reports early findings, without long-term oncologic outcomes, the results are consistently encouraging. Training programs have already yielded successes. Indeed, multiple institutions have shown that transoral robotic surgery programs can be successfully established yielding excellent clinical outcomes. In addition, early studies of swallowing function following transoral robotic surgery show swallowing outcomes that are superior to some of the reported chemoradiation results for equivalent lesions.

Prediction of response to chemoradiation therapy in squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Tumor microenvironment, including blood flow and permeability, may provide crucial information regarding response to chemoradiation therapy. Thus, the objective of this study was to investigate the efficacy of pretreatment DCE-MR imaging for prediction of response to chemoradiation therapy in HNSCC. MATERIALS AND METHODS: DCE-MR imaging studies were performed on 33 patients with newly diagnosed HNSCC before neoadjuvant chemoradiation therapy by using a 1.5T (n = 24) or a 3T (n = 9) magnet. The data were analyzed by using SSM for estimation of Ktrans, ve, and τi. Response to treatment was determined on completion of chemoradiation as CR, with no evidence of disease (clinically or pathologically), or PR, with pathologically proved residual tumor. RESULTS: The average pretreatment Ktrans value of the CR group (0.64 ± 0.11 minutes−1, n = 24) was significantly higher (P = .001) than that of the PR (0.21 ± 0.05 minutes−1, n = 9) group. No significant difference was found in other pharmacokinetic model parameters: ve and τi, between the 2 groups. Although the PR group had larger metastatic nodal volume than the CR group, it was not significantly different (P = .276). CONCLUSIONS: These results indicate that pretreatment DCE-MR imaging can be potentially used for prediction of response to chemoradiation therapy of HNSCC.

Transoral Robotic Surgery Alone for Oropharyngeal Cancer: An Analysis of Local Control

OBJECTIVE To evaluate local control following transoral robotic surgery (TORS) with the da Vinci Surgical System (Intuitive Surgical Inc) as a single treatment modality for oropharyngeal squamous cell carcinoma (OSCC). DESIGN Prospective, single-center, observational study. SETTING Academic university health system and tertiary referral center. PATIENTS Thirty adults with previously untreated OSCC. INTERVENTION Transoral robotic surgery with staged neck dissection as indicated. MAIN OUTCOME MEASURES Local control and margin status. RESULTS Thirty patients were enrolled with previously untreated OSCC and no prior head and neck radiation therapy. Follow-up duration was at least 18 months. At the time of diagnosis, 9 tumors were T1 (30%); 16 were T2 (53%); 4 were T3 (13%); and 1 was T4a (3%). The anatomic sites of these primary tumors were tonsil in 14 (47%), tongue base in 9 (30%), glossotonsillar sulcus in 3 (10%), soft palate in 3 (10%), and oropharyngeal wall in 1 (3%). There was only 1 patient (3%) who had a positive margin after primary resection; further resection achieved a final negative margin. Perineural invasion was noted in 3 tumors (10%). No patient received postoperative adjuvant therapy. At a mean follow-up of 2.7 years (range, 1.5-5.1 years), there was 1 patient with local failure (3%). CONCLUSION As the only modality used for treatment of pathologically low-risk OSCCs, TORS provides high local control and is associated with low surgical morbidity.

Selective neck dissection and deintensified postoperative radiation and chemotherapy for oropharyngeal cancer: A subset analysis of the university of pennsylvania transoral robotic surgery trial†

The purpose of this study was to determine the regional recurrence rate of node‐positive oropharyngeal squamous cell carcinoma (OPSCC) in patients undergoing transoral robotic surgery (TORS) and selective neck dissection (SND) followed by observation, radiation, or concurrent chemoradiation.

Transoral robotic surgery for oropharyngeal carcinoma and its impact on patient-reported quality of life and function

The aim of this study was to assess the quality of life of patients with oropharyngeal squamous cell carcinoma after transoral robotic surgery (TORS).

Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study

This pilot study explores the potential of noninvasive diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) for monitoring early relative blood flow (rBF), tissue oxygen saturation (StO(2)), and total hemoglobin concentration (THC) responses to chemo-radiation therapy in patients with head and neck tumors. rBF, StO(2), and THC in superficial neck tumor nodes of eight patients are measured before and during the chemo-radiation therapy period. The weekly rBF, StO(2), and THC kinetics exhibit different patterns for different individuals, including significant early blood flow changes during the first two weeks. Averaged blood flow increases (52.7+/-9.7)% in the first week and decreases (42.4+/-7.0)% in the second week. Averaged StO(2) increases from (62.9+/-3.4)% baseline value to (70.4+/-3.2)% at the end of the second week, and averaged THC exhibits a continuous decrease from pretreatment value of (80.7+/-7.0) [microM] to (73.3+/-8.3) [microM] at the end of the second week and to (63.0+/-8.1) [microM] at the end of the fourth week of therapy. These preliminary results suggest daily diffuse-optics-based therapy monitoring is feasible during the first two weeks and may have clinical promise.

Epidermal growth factor receptor inhibition modulates the microenvironment by vascular normalization to improve chemotherapy and radiotherapy efficacy.

Background Epidermal growth factor receptor (EGFR) inhibitors have shown only modest clinical activity when used as single agents to treat cancers. They decrease tumor cell expression of hypoxia-inducible factor 1-α (HIF-1α) and vascular endothelial growth factor (VEGF). Hypothesizing that this might normalize tumor vasculature, we examined the effects of the EGFR inhibitor erlotinib on tumor vascular function, tumor microenvironment (TME) and chemotherapy and radiotherapy sensitivity. Methodology/Principal Findings Erlotinib treatment of human tumor cells in vitro and mice bearing xenografts in vivo led to decreased HIF-1α and VEGF expression. Treatment altered xenograft vessel morphology assessed by confocal microscopy (following tomato lectin injection) and decreased vessel permeability (measured by Evans blue extravasation), suggesting vascular normalization. Erlotinib increased tumor blood flow measured by Power Doppler ultrasound and decreased hypoxia measured by EF5 immunohistochemistry and tumor O2 saturation measured by optical spectroscopy. Predicting that these changes would improve drug delivery and increase response to chemotherapy and radiation, we performed tumor regrowth studies in nude mice with xenografts treated with erlotinib and either radiotherapy or the chemotherapeutic agent cisplatin. Erlotinib therapy followed by cisplatin led to synergistic inhibition of tumor growth compared with either treatment by itself (p<0.001). Treatment with erlotinib before cisplatin led to greater tumor growth inhibition than did treatment with cisplatin before erlotinib (p = 0.006). Erlotinib followed by radiation inhibited tumor regrowth to a greater degree than did radiation alone, although the interaction between erlotinib and radiation was not synergistic. Conclusions/Significance EGFR inhibitors have shown clinical benefit when used in combination with conventional cytotoxic therapy. Our studies show that targeting tumor cells with EGFR inhibitors may modulate the TME via vascular normalization to increase response to chemotherapy and radiotherapy. These studies suggest ways to assess the response of tumors to EGFR inhibition using non-invasive imaging of the TME.