Background
Fluorescence imaging hardware (SPY) has recently been developed for intraoperative assessment of blood flow via detection of probes emitting in the near-infrared (NIR) spectrum. This study ...sought to determine if this imaging system was capable of detecting micrometastatic head and neck squamous cell carcinoma (HNSCC) in preclinical models.
Methods
A NIR fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody targeting epidermal growth factor receptor (EGFR; panitumumab) or nonspecific IgG. HNSCC flank (SCC-1) and orthotopic (FADU and OSC19) xenografts were imaged 48–96 h after systemic injection of labeled panitumumab or IgG. The primary tumor and regional lymph nodes were dissected using fluorescence guidance with the SPY system and grossly assessed with a charge-coupled NIR system (Pearl). Histologic slides were also imaged with a NIR charged-coupled device (Odyssey) and fluorescence intensity was correlated with pathologic confirmation of disease.
Results
Orthotopic tongue tumors were clearly delineated from normal tissue with tumor-to-background ratios of 2.9 (Pearl) and 2.3 (SPY). Disease detection was significantly improved with panitumumab-IRDye compared to IgG-IRDye800 (
P
< 0.05). Tissue biopsy samples (average size 3.7 mm) positive for fluorescence were confirmed for pathologic disease by histology and immunohistochemistry (
n
= 25 of 25). Biopsy samples of nonfluorescent tissue were proven to be negative for malignancy (
n
= 28 of 28). The SPY was able to detect regional lymph node metastasis (<1.0 mm) and microscopic areas of disease. Standard histological assessment in both frozen and paraffin-embedded histologic specimens was augmented using the Odyssey.
Conclusions
Panitumumab-IRDye800 may have clinical utility in detection and removal of microscopic HNSCC using existing intraoperative optical imaging hardware and may augment analysis of frozen and permanent pathology.
Mammary analog secretory carcinoma (MASC) is a recently recognized low-grade salivary carcinoma characterized by a specific ETV6 rearrangement. We describe 14 new MASCs and examine their ...immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin and S100, were demonstrated in 11/11, 14/14, and 12/14 MASCs, respectively. All low-grade salivary duct carcinomas coexpressed S100/mammaglobin (6/6); none harbored ETV6 rearrangements (0/5). Given that S100/mammaglobin coexpression and absence of zymogen granules are features of both MASC and low-grade salivary duct carcinoma, these two are best distinguished histologically. The former is predominantly an extraductal neoplasm with bubbly pink cytoplasm, whereas the latter is a distinct intraductal micropapillary and cribriform process. Querying ETV6 gene status may be necessary for difficult cases. No acinic cell carcinoma expressed mammaglobin (0/13) or harbored an ETV6 rearrangement (0/7); only 1/13 acinic cell carcinomas weakly expressed S100. DOG1 expression was limited or absent among all tumor types, except acinic cell carcinoma which expressed DOG1 diffusely in a canalicular pattern. Therefore, histology and immunohistochemistry (mammaglobin, S100, DOG1) suffices in distinguishing acinic cell carcinoma from both MASC and low-grade salivary duct carcinoma. HER2 (ERBB2) amplification was detected in only 1/10 acinic cell carcinomas, but none of the MASCs or low-grade salivary duct carcinomas tested. High-grade salivary duct carcinomas frequently expressed mammaglobin (11/18) and harbored HER2 amplifications (13/15); none harbored ETV6 rearrangements (0/12). High-grade salivary duct carcinomas can easily be distinguished from these other entities by histology and HER2 amplification.
No consensus exists as to the best technique, or techniques, to optimize wound healing, decrease pharyngocutaneous fistula formation, and shorten both hospital length of stay and time to initiation ...of oral intake after salvage laryngectomy. We sought to combine the recent experience of multiple high-volume institutions, with different reconstructive preferences, in the management of pharyngeal closure technique for post-radiation therapy salvage total laryngectomy in an effort to bring clarity to this clinical challenge.
To determine if the use of vascularized flaps in either an onlay or interposed fashion reduces the incidence or duration of pharyngocutaneous fistula after salvage laryngectomy compared with simple primary closure of the pharynx.
Multi-institutional retrospective review of all patients undergoing total laryngectomy after having received definitive radiation therapy with or without chemotherapy between January 2005 and January 2012, conducted at 7 academic medical centers.
Academic, tertiary referral centers.
The study population comprised 359 patients from 8 institutions. All patients had a history of laryngeal irradiation and underwent laryngectomy between 2005 and 2012. They were grouped as primary closure, pectoralis myofascial onlay flap, or interposed free tissue. All patients had a minimum of 4 months follow-up.
Fistula incidence, severity, and predictors of fistula.
Of the 359 patients, fistula occurred in 94 (27%). For patients with fistula, hospital stay increased from 8.9 to 12.1 days (P < .001) and oral diet initiation was delayed from 10.5 days to 29.9 days (P < .001). Patients were grouped according to closure technique: primary closure (n = 99), pectoralis onlay flap (n = 40), and interposed free tissue (n = 220). Incidence of fistula with primary closure was 34%. For the interposed free flap group, the fistula rate was lower at 25% (P = .07). Incidence of fistula was the lowest for the pectoralis onlay group at 15% (P = .02). Multivariate analysis confirmed a significantly lower fistula rate with either flap technique. For patients who developed fistula, mean duration of fistula was significantly prolonged with primary closure (14.0 weeks) compared with pectoralis flap (9.0 weeks) and free flap (6.5 weeks).
Pharyngocutaneous fistula remains a significant problem following salvage laryngectomy. Use of nonirradiated, vascularized flaps reduced the incidence and duration of fistula and should be considered during salvage laryngectomy.
Purpose
Though various targets have been proposed and evaluated, no agent has yet been investigated in a clinical setting for head and neck cancer. The present study aimed to compare two ...fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibodies for detection of head and neck squamous cell carcinoma (HNSCC).
Procedures
Antigen specificities and
in vitro
imaging of the fluorescently labeled anti-EGFR antibodies were performed. Next, immunodeficient mice (
n
= 22) bearing HNSCC (OSC-19 and SCC-1) tongue tumors received systemic injections of cetuximab-IRDye800CW, panitumumab-IRDye800CW, or IgG-IRDye800CW (a nonspecific control). Tumors were imaged and resected using two near-infrared imaging systems, SPY and Pearl. Fluorescent lymph nodes were also identified, and all resected tissues were sent for pathology.
Results
Panitumumab-IRDye800CW and cetuximab-IRDye800CW had specific and high affinity binding for EGFR (
K
D
= 0.12 and 0.31 nM, respectively). Panitumumab-IRDye800CW demonstrated a 2-fold increase in fluorescence intensity compared to cetuximab-IRDye800CW
in vitro
.
In vivo
, both fluorescently labeled antibodies produced higher tumor-to-background ratios compared to IgG-IRDye800CW. However, there was no significant difference between the two in either cell line or imaging modality (OSC-19:
p
= 0.08 SPY,
p
= 0.48 Pearl; SCC-1:
p
= 0.77 SPY,
p
= 0.59 Pearl; paired
t
tests).
Conclusions
There was no significant difference between the two fluorescently labeled anti-EGFR monoclonal antibodies in murine models of HNSCC. Both cetuximab and panitumumab can be considered suitable targeting agents for fluorescent intraoperative detection of HNSCC.
Background
Perioperative management of advanced osteoradionecrosis of the head and neck requiring free flap (FF) reconstruction varies. Our objectives included assessment of practice patterns and ...outcomes.
Methods
Multi‐institutional, retrospective review of FF reconstruction for head and neck osteoradionecrosis (n = 260).
Results
Administration of preoperative antibiotics did not correlate with reduction in postoperative complications. Preoperative alcohol use correlated with higher rates of hardware exposure (p = 0.03) and 30‐day readmission (p = 0.04). Patients with FF compromise had higher TSH (p = 0.04) and lower albumin levels (p = 0.005). Prealbumin levels were lower in patients who required neck washouts (p = 0.02) or a second FF (p = 0.03). TSH levels were higher in patients undergoing postoperative debridement (p = 0.03) or local flap procedures (p = 0.04).
Conclusion
Malnutrition, hypothyroidism, and substance abuse correlated with a higher incidence of postoperative wound complications in patients undergoing FF reconstruction for advanced osteoradionecrosis. Preoperative antibiotics use did not correlate with a reduction in postoperative wound complications.
Identify predictors of overall survival (OS) after hypopharyngeal/laryngeal cancer in Florida.
We conducted a retrospective cohort study using data from the Florida Cancer Data System (FCDS) on ...patients diagnosed with hypopharyngeal or laryngeal cancer from 2010-2017. Primary outcome was OS. Hazard ratios (HRs) were estimated from univariable and multivariable Cox regression models for OS. Data was analyzed from November 1, 2022, to June 30, 2023.
We analyzed 6771 patients, who were primarily male (81.2%), White non-Hispanic (WNH) (78.2%), publicly insured (70.1%), married (51.8%), and residents of urban counties (73.6%). Black patients were more likely to be younger at diagnosis (38.9%), single (43.4%), to have distant SEER stage disease (25.6%). Median OS were lowest among patients who were uninsured (34 months), with hypopharyngeal site disease (18 months), and a smoking history (current: 34 months, former: 46 months, no smoking: 63 months). Multivariable Cox regression analysis showed worse OS for single/unmarried vs married (HR 1.47 95%CI: 1.36-1.59,
< .001), history of tobacco use (current: HR 1.62 95%CI: 1.440-1.817,
< .001; former smokers: (HR 1.28 95%CI: 1.139-1.437,
< .001) vs no history). Improved OS was observed among White Hispanics (WH) vs WNH (HR .73 95%CI: .655-.817,
< .001) and women vs men (HR .88 95%CI: .807-.954,
= .002). Geographical mapping showed that mortality rates were highest in census tracts with low income and education.
Our findings suggest that sociodemographic and clinical factors impact OS from hypopharyngeal/laryngeal cancer in Florida and vary geographically within the state. These results will help guide future public health interventions.
Objective
Evaluate if vascular normalization with an antiangiogenic monoclonal antibody improves detection of melanoma using fluorescently labeled antibody‐based imaging.
Study Design
Preclinical.
...Methods
Panitumumab and control IgG were covalently linked to a near‐infrared fluorescent probe (IRDye800CW). Immunodeficient mice with ear xenografts of melanoma cell lines (A375 and SKMEL5) were systemically injected (200 μg, tail vein) with either IgG‐IRDye800CW, panitumumab‐IRDye800CW, or a combination (bevacizumab 5mg/kg, administered 72 hours prepanitumumab‐IRDye800CW) (n = 5). Primary tumors were imaged with open‐field (LUNA, Novadaq, Toronto, Ontario, Canada) and closed‐field (Pearl, LI‐COR Biosciences, Lincoln, NB) imaging devices. Postresection, the concentration of labeled antibody within the tumor (μg/g) was calculated using normalized standards.
Results
The mean fluorescence within the melanoma tumors was greater for the combination group compared to panitumumab alone for both cell lines (P < 0.001). The tumor‐to‐background ratio (TBR) for the A375 tumors was greater for the combination (3.4–7.1) compared to the panitumumab alone (3.2–5.0) (P = 0.04). The TBR for SKMEL5 tumors was greater for the combination (2.4–6.0) compared to the panitumumab alone (2.2–3.9) (P = 0.02). Within A375 tumors, the concentration was lower for panitumumab (0.51 μg/g) compared to combination group (0.68 μg/g) (P = 0.036). Within SKMEL5 tumors, the concentration was lower for panitumumab (0.0.17 μg/g) compared to combination group (0.35 μg/g) (P = 0.048). Residual tumor (1.0–0.2 mg) could be differentiated from background in both panitumumab and combination groups. For both cell lines, panitumumab and combination groups had greater mean fluorescence of the tumor compared to control IgG.
Conclusion
The addition of antiangiogenic therapy improves uptake of fluorescently labeled monoclonal antibodies within melanoma tumors. Clinical translation could improve detection of melanoma intraoperatively, reducing positive margins and sparing normal tissue.
Level of Evidence
NA Laryngoscope, 126:E387–E395, 2016
Postlaryngectomy stricture formation and dysphagia negatively affect quality of life and result in nutritional compromise. Understanding risk factors and successful treatment strategies may improve ...treatment outcomes.
Historical cohort study.
Tertiary care medical center.
Patients at a tertiary care center who underwent a total laryngectomy between 2003 and 2009 (N = 263) were evaluated in a retrospective manner. Patient demographics, comorbidities, tobacco and alcohol usage, dietary outcomes, feeding tube dependence, and treatment modalities were assessed. Management strategies and outcomes were evaluated.
Strictures developed in 19% (n = 49) of patients, and the majority (82%) occurred in the first year. Incidences of stricture formation were similar for primary (19%) and salvage laryngectomy (19%) patients. Patients undergoing salvage laryngectomy were 2 times more likely to be reconstructed with a free flap, whereas those undergoing a primary laryngectomy were 3 times more likely to be closed primarily. Tubed flap reconstruction significantly increased the incidence of stricture formation compared to primary closure (P = .02) in salvage laryngectomy cases. In primary laryngectomy patients, stricture formation did not correlate with flap reconstruction (P = .34) or adjuvant radiation therapy (P = .79). Patients who required a single dilation had better dietary outcomes compared to patients who required serial dilations (P = .14). There was no difference in overall disease-free survival in primary vs salvage laryngectomy patients (P = .95).
Rates of stricture formation were the same in patients undergoing salvage compared to primary total laryngectomy.
Purpose of Review
The design of novel herpes simplex type I (HSV-1)–derived oncolytic virotherapies is a balancing act between safety, immunogenicity, and replicative potential. We have undertaken ...this review to better understand how these considerations can be incorporated into rational approaches to the design of novel herpesvirus oncolytic virotherapies.
Recent Findings
Several recent papers have demonstrated that enhancing the potential of HSV-1 oncolytic viruses to combat anti-viral mechanisms present in the tumor microenvironment leads to greater efficacy than their parental viruses.
Summary
It is not entirely clear how the immunosuppressive tumor microenvironment affects oncolytic viral replication and spread within tumors. Recent work has shown that the manipulation of specific cellular and molecular mechanisms of immunosuppression operating within the tumor microenvironment can enhance the efficacy of oncolytic virotherapy. We anticipate that future work will integrate greater knowledge of immunosuppression in tumor microenvironments with design of oncolytic virotherapies.
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