Laura A. Smit

Unknown primary head and neck squamous cell carcinoma in the era of fluorodeoxyglucose-positron emission tomography/CT and intensity-modulated radiotherapy

The diagnosis and treatment of head and neck carcinoma of unknown primary (CUP) have changed with the introduction of fluorodeoxyglucose‐positron emission tomography (FDG‐PET)/CT and intensity‐modulated radiotherapy (IMRT), with potential implications for outcome.

Physiologic distribution of PSMA-ligand in salivary glands and seromucous glands of the head and neck on PET/CT

OBJECTIVES Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is used for detection and (re)staging of prostate cancer. However, healthy salivary, seromucous, and lacrimal glands also have high PSMA-ligand uptake. This study aimed to describe physiologic PSMA-ligand uptake distribution characteristics in the head and neck to aid in PSMA PET/CT interpretation and to identify possible new clinical applications for PSMA-ligand imaging. STUDY DESIGN Thirty consecutive patients who underwent PSMA PET/CT for prostate cancer were evaluated. Tracer maximum standardized uptake values (SUVmax) in the salivary, seromucous, and lacrimal glands were determined visually and quantitatively. Overall and intraindividual variations were reported. RESULTS All gland locations had increased tracer uptake. The mean SUVmax ± standard deviation varied: parotid 12.3 ± 3.9; submandibular 11.7 ± 3.5; sublingual 4.5 ± 1.9; soft palate 2.4 ± 0.5; pharyngeal wall 4.3 ± 1.3; nasal mucosa 3.4 ± 0.9; supraglottic larynx 2.7 ± 0.7; and lacrimal 6.2 ± 2.2. The parotid had the largest overall variation in SUVmax (5.2-22.9), and the sublingual glands had the largest mean intraindividual difference (18.1%). CONCLUSIONS Major and minor salivary and seromucous glands consistently have high PSMA-ligand uptake. Minor gland locations can be selectively visualized by this technique for the first time. This provides potential new applications such as quantification of present salivary gland tissues and individualization of radiotherapy for head and neck cancer or lutetium-177-PSMA radionuclide treatment.

Clinicopathological characteristics and outcome of 31 patients with ETV6-NTRK3 fusion gene confirmed (mammary analogue) secretory carcinoma of salivary glands

OBJECTIVES In 2010, a new subtype of salivary gland cancer (SGC), (mammary analogue) secretory carcinoma (SC), was defined, characterized by the ETV6-NTRK3 fusion gene. As clinical behavior and outcome data of this histological subtype tumor are still sparse, we aimed to describe the clinicopathological course and outcome of a series of translocation positive SC patients. PATIENT AND METHODS We re-evaluated the pathological diagnosis of a subset of SGCs, diagnosed in 4 of 8 Dutch head and neck centers. Subsequently, tumors with a morphological resemblance to SC were tested for the ETV6-NTRK3 fusion gene using RT-PCR. Furthermore, patients prospectively diagnosed with SC were included. The clinical characteristics and outcomes were retrieved from the patient files. RESULTS Thirty-one patients with ETV6-NTRK3 fusion gene positive SC were included. The median age was 49 years, 17 patients (55%) were male. Eighteen tumors (58%) arose in the parotid gland. One patient presented with lymph node metastasis. All patients underwent tumor resection and 4 patients had a neck dissection. Four patients had re-resection and 15 patients (48%) received postoperative radiotherapy. One patient developed a local recurrence, no regional recurrences or distant metastases were observed. After a median follow-up of 49 months the 5- and 10-year overall survival were 95%, the 5- and 10-year disease free survival were 89%. CONCLUSION The clinical course of SC is favorable with a low rate of locoregional recurrence and excellent survival. Given the low incidence of nodal metastases, elective neck treatment, i.e. surgery and/or radiotherapy, does not seem to be indicated.

Near infrared hyperspectral imaging to evaluate tongue tumor resection margins intraoperatively (Conference Presentation)

Positive tumor resection margins are reported in up to 45% of the patients undergoing surgery for tongue cancer. With the aim to develop a technique that can assess tumor resection margins intraoperatively, we conducted an ex vivo study to evaluate the feasibility of near infrared hyperspectral imaging for distinguishing tumor from healthy tongue tissue. Fresh surgical specimens of squamous cell carcinoma of the tongue were scanned with a pushbroom camera. The acquired spectral hypercubes contain a measure of the diffuse light reflectance (wavelength range of 900-1700 nm) for each pixel of the hyperspectral image. Spectral bands were selected from the spectrum and used to classify spectra of tumor and healthy tissue. In this, a linear classifier was trained on 80% of the data and its performance in predicting the tissue type of the residual 20% of the data was measured. This was repeated five times and mean accuracy, sensitivity and specificity were used as output for this study. A total of 463 spectra were obtained from tongue tumor tissue and 421 spectra from healthy tongue tissue. The spectral bands between 1060-1130 nm and 1150-1190 nm were used in the classification analysis. Mean accuracy, sensitivity and specificity were 89%±13, 94%±11 and 87%±21, respectively. Near infrared hyperspectral imaging can discriminate tongue tumor tissue from healthy tongue tissue in an ex vivo setting by using specific bands of the reflectance spectrum. Further analyses will be done to assess whether using the whole spectrum can improve the classification results.

Salivary duct carcinoma: evaluation of treatment and outcome in a tertiary referral institute

PurposeThe aggressive behavior of salivary duct carcinoma (SDC) necessitates an aggressive treatment strategy, including surgery and radiotherapy (RT). We evaluated practice patterns and treatment outcomes in patients with SDC treated in our Institute.MethodsPatients with SDC of the parotid or submandibular gland treated with curative intention in our Institute from 1998 until 2016 were reviewed. Our diagnostic workup and treatment strategy were evaluated together with treatment outcomes.ResultsFifteen patients with SDC were included. Staging included MRI and ultrasound-guided fine needle aspiration cytology. Only in a minority (20%) of patients, the preoperative diagnosis of SDC was raised due to positive immunohistochemical staining for the androgen receptor (AR) on cytology. All patients were treated with (sub)total resection of the salivary gland and 53% underwent a therapeutic neck dissection. All patients except one received postoperative RT. Immunohistochemical staining was found positive for AR (100%) and human epidermal growth factor receptor 2 (HER2/neu) (13%). No local recurrences occurred. Regional and distant failure rates were 20% and 40%, respectively.ConclusionsExcellent local control rates can be achieved with extensive (local) surgical treatment and postoperative RT. In case of lymph node metastases, a neck dissection with adjuvant postoperative RT is warranted. In patients with node-negative disease, a less aggressive approach for the neck seems feasible to reduce treatment-related morbidity.

Trends in treatment, incidence and survival of hypopharynx cancer: a 20-year population-based study in the Netherlands

Hypopharynx cancer has the worst prognosis of all head and neck squamous cell cancers. Since the 1990s, a treatment shift has appeared from a total laryngectomy towards organ preservation therapies. Large randomized trials evaluating treatment strategies for hypopharynx cancer, however, remain scarce, and frequently this malignancy is evaluated together with larynx cancer. Therefore, our aim was to determine trends in incidence, treatment and survival of hypopharynx cancer. We performed a population-based cohort study including all patients diagnosed with T1–T4 hypopharynx cancer between 1991 and 2010 in the Netherlands. Patients were recorded by the national cancer registry database and verified by a national pathology database. 2999 patients were identified. The incidence increased significantly with 4.1% per year until 1997 and decreased non-significantly afterwards. For women, the incidence increased with 1.7% per year during the entire study period. Total laryngectomy as primary treatment significantly decreased, whereas radiotherapy and chemoradiation increased. The 5-year overall survival significantly increased from 28% in 1991–2000 to 34% in 2001–2010. Overall survival for T3 was equal for total laryngectomy and (chemo)radiotherapy, but for T4-patients the survival was significantly better after primary total laryngectomy (± adjuvant radiotherapy). This large population-based study demonstrates a shift in treatment preference towards organ preservation therapies. The 5-year overall survival increased significantly in the second decade. The assumed equivalence of organ preservation and laryngectomy may require reconsideration for T4 disease.

Diffuse reflectance spectroscopy from 400-1600 nm to evaluate tumor resection margins during head and neck surgery (Conference Presentation)

This ex vivo study evaluates the feasibility of diffuse reflectance spectroscopy (DRS) for discriminating tumor from healthy oral tissue, with the aim to develop a technique that can be used to determine a complete excision of tumor through intraoperative margin assessment. DRS spectra were acquired on fresh surgical specimens from patients with an oral squamous cell carcinoma. The spectra represent a measure of diffuse light reflectance (wavelength range of 400-1600 nm), detected after illuminating tissue with a source fiber at 1.0 and 2.0 mm distances from a detection fiber. Spectra were obtained from 23 locations of tumor tissue and 16 locations of healthy muscle tissue. Biopsies were taken from all measured locations to facilitate an optimal correlation between spectra and pathological information. The area under the spectrum was used as a parameter to classify spectra of tumor and healthy tissue. Next, a receiver operating characteristics (ROC) analysis was performed to provide the area under the receiver operating curve (AUROC) as a measure for discriminative power. The area under the spectrum between 650 and 750 nm was used in the ROC analysis and provided AUROC values of 0.99 and 0.97, for distances of 1 mm and 2 mm between source and detector fiber, respectively. DRS can discriminate tumor from healthy oral tissue in an ex vivo setting. More specimens are needed to further evaluate this technique with component analyses and classification methods, prior to in vivo patient measurements.