Anthony Morlandt

Safety and Tumor-specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer

Purpose: Positive margins dominate clinical outcomes after surgical resections in most solid cancer types, including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that EGFR can be targeted for safe and specific real-time localization of cancer. Experimental Design: A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n = 12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days after infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology. Results: There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-to-background ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathologic analysis of tissues ex vivo. Fluorescence levels positively correlated with EGFR levels. Conclusions: We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology. Clin Cancer Res; 21(16); 3658–66. ©2015 AACR.

Early Oral Tongue Squamous Cell Carcinoma: Sampling of Margins From Tumor Bed and Worse Local Control

IMPORTANCE Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique. OBJECTIVE To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC. DESIGN, SETTING, AND PARTICIPANTS A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015. INTERVENTIONS In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR. MAIN OUTCOMES AND MEASURES Local recurrence. RESULTS Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin. CONCLUSIONS AND RELEVANCE The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen-based margin assessment is recommended.

Safety and efficacy of intra-articular infliximab therapy for treatment-resistant temporomandibular joint arthritis in children: a retrospective study

OBJECTIVE TM joint (TMJ) arthritis occurs in up to 80% of children with JIA and can result in substantial deformity. TMJ arthritis can be refractory to systemic immunosuppressive therapy and IA CS injections (IACIs). Multiple studies have shown the benefit of IA infliximab injections (IAIIs) in several different joints, so we used intra-articular infliximab injections (IAIIs) in JIA patients with TMJ arthritis refractory to IACIs. The objective of the study was to test the safety and efficacy of IAII therapy for TMJ arthritis. METHODS Retrospective chart review was performed for all children with JIA treated at a single centre who received one or more IAIIs. Outcomes assessed were safety of the injections as well as efficacy as evidenced by maximal incisal opening (MIO) and MRI findings. RESULTS Twenty-four children underwent bilateral IAIIs, all of whom had at least one follow-up visit after the final injection. All 24 tolerated the injections without any adverse events. MIOs were unchanged in patients before and after IAII. Findings of acute synovitis were present in 30/46 (65%) TMJs at baseline, 44/48 (92%) following completion of the IACI and 42/48 (88%) following completion of the IAII; findings of chronic synovitis at the three time points were 12/46 (26%), 29/48 (60%) and 38/48 (79%). Resolution of the arthritis was observed in six TMJs. CONCLUSION IAII was safe and it reversed the progression of TMJ arthritis in some patients with refractory disease. Future studies will evaluate the efficacy of infliximab vs CS injections as initial therapy for TMJ arthritis.

A ratiometric threshold for determining presence of cancer during fluorescence-guided surgery.

Fluorescence‐guided imaging to assist in identification of malignant margins has the potential to dramatically improve oncologic surgery. However, a standardized method for quantitative assessment of disease‐specific fluorescence has not been investigated. Introduced here is a ratiometric threshold derived from mean fluorescent tissue intensity that can be used to semi‐quantitatively delineate tumor from normal tissue.

Characterizing the Utility and Limitations of Repurposing an Open-Field Optical Imaging Device for Fluorescence-Guided Surgery in Head and Neck Cancer Patients

The purpose of this study was to assess the potential of U.S. Food and Drug Administration–cleared devices designed for indocyanine green–based perfusion imaging to identify cancer-specific bioconjugates with overlapping excitation and emission wavelengths. Recent clinical trials have demonstrated potential for fluorescence-guided surgery, but the time and cost of the approval process may impede clinical translation. To expedite this translation, we explored the feasibility of repurposing existing optical imaging devices for fluorescence-guided surgery. Methods: Consenting patients (n = 15) scheduled for curative resection were enrolled in a clinical trial evaluating the safety and specificity of cetuximab-IRDye800 (NCT01987375). Open-field fluorescence imaging was performed preoperatively and during the surgical resection. Fluorescence intensity was quantified using integrated instrument software, and the tumor-to-background ratio characterized fluorescence contrast. Results: In the preoperative clinic, the open-field device demonstrated potential to guide preoperative mapping of tumor borders, optimize the day of surgery, and identify occult lesions. Intraoperatively, the device demonstrated robust potential to guide surgical resections, as all peak tumor-to-background ratios were greater than 2 (range, 2.2–14.1). Postresection wound bed fluorescence was significantly less than preresection tumor fluorescence (P < 0.001). The repurposed device also successfully identified positive margins. Conclusion: The open-field imaging device was successfully repurposed to distinguish cancer from normal tissue in the preoperative clinic and throughout surgical resection. This study illuminated the potential for existing open-field optical imaging devices with overlapping excitation and emission spectra to be used for fluorescence-guided surgery.

Fluorescence Imaging for Cancer Screening and Surveillance

The advent of fluorescence imaging (FI) for cancer cell detection in the field of oncology is promising for both cancer screening and surgical resection. Particularly, FI in cancer screening and surveillance is actively being evaluated in many new clinical trials with over 30 listed on Clinical Trials.gov. While surgical resection forms the foundation of many oncologic treatments, early detection is the cornerstone for improving outcomes and reducing cancer-related morbidity and mortality. The applications of FI are twofold as it can be applied to high-risk patients in addition to those undergoing active surveillance. This technology has the promise of highlighting lesions not readily detected by conventional imaging or physical examination, allowing disease detection at an earlier stage of development. Additionally, there is a persistent need for innovative, cost-effective imaging modalities to ameliorate healthcare disparities and the global burden of cancer worldwide. In this review, we outline the current utility of FI for screening and detection in a range of cancer types.

Reconstruction of midface defects with the osteocutaneous radial forearm flap: Evaluation of long term outcomes including patient reported quality of life

Maxillectomy defects significantly impair quality of life. Prosthetics can overcome some of these issues, but has limitations. The role of the osteocutaneous radial forearm free flap (OC‐RFFF) has been established for reconstruction of smaller maxillectomy defects, but its role in larger defects is not well defined. We aim to evaluate outcomes after midface reconstruction utilizing the OC‐RFFF.

Retracted: Worst Pattern Of Invasion and occult cervical metastases for oral squamous carcinoma

The above article, published online in Wiley Online Library as the Version of Record on March 28, 2017 (doi 10.1002/hed.24754), has been retracted by agreement between the Editor-in-Chief, Ehab Y. Hanna, and Wiley Periodicals, Inc. The retraction has been agreed owing to a dispute as to authorship and inclusion of some data in the analysis. REFERENCE Velosa, C., Shi, Q., Stevens, T. M., Chiosea, S. I., Purgina, B., Carroll, W., Rosenthal, E., Morlandt, A., Loree, T. and Brandwein-Weber, M. S. (2017), Worst pattern of invasion and occult cervical metastases for oral squamous carcinoma. Head Neck. doi:10.1002/hed.24754.

Retracted: Worst Pattern Of Invasion and occult cervical metastases for oral squamous carcinoma: Update on impact of adjuvant rt for low-stage high-risk oral squamous cancer

The above article, published online in Wiley Online Library as the Version of Record on March 28, 2017 (doi 10.1002/hed.24754), has been retracted by agreement between the Editor-in-Chief, Ehab Y. Hanna, and Wiley Periodicals, Inc. The retraction has been agreed owing to a dispute as to authorship and inclusion of some data in the analysis. REFERENCE Velosa, C., Shi, Q., Stevens, T. M., Chiosea, S. I., Purgina, B., Carroll, W., Rosenthal, E., Morlandt, A., Loree, T. and Brandwein-Weber, M. S. (2017), Worst pattern of invasion and occult cervical metastases for oral squamous carcinoma. Head Neck. doi:10.1002/hed.24754.

Worst Pattern Of Invasion and occult cervical metastases for oral squamous carcinoma

The above article, published online in Wiley Online Library as the Version of Record on March 28, 2017 (doi 10.1002/hed.24754), has been retracted by agreement between the Editor-in-Chief, Ehab Y. Hanna, and Wiley Periodicals, Inc. The retraction has been agreed owing to a dispute as to authorship and inclusion of some data in the analysis. REFERENCE Velosa, C., Shi, Q., Stevens, T. M., Chiosea, S. I., Purgina, B., Carroll, W., Rosenthal, E., Morlandt, A., Loree, T. and Brandwein-Weber, M. S. (2017), Worst pattern of invasion and occult cervical metastases for oral squamous carcinoma. Head Neck. doi:10.1002/hed.24754.