Tilmanocept as a novel tracer for lymphatic mapping and sentinel lymph node biopsy in melanoma and oral cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been pivotal for pathological assessment of nodal status in cutaneous melanoma (CM) and oral cavity squamous cell carcinoma (OCSCC) thus crucial for staging. An ideal agent for lymphatic mapping should have a standardized preparation, appropriate accumulation in first-echelon nodes and no side effects. Tilmanocept, a CD206-receptor targeted novel radiotracer fulfils these properties. This study investigated Tilmanocept for lymphoscintigraphy and intraoperative identification of sentinel lymph nodes (SLN) in CM and OCSCC. METHODS: This prospective cross sectional study examined patients who presented to Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney. Patients had biopsy proven tumours with clinically and radiologically negative regional lymph nodes. Tilmanocept guided lymphoscintigraphy was followed by intraoperative SLNs identification via handheld gamma probe. Primary endpoints were detection and retrieval rate of SLNs while secondary endpoints included pathological status of SLNs. RESULTS: Thirty-five patients were included (26 with CM and 9 with OCSCC) with the most common primary tumour site for CM on the extremities (33.3%). Lymphoscintigraphy with Tilmanocept identified at least 1 SLN (sensitivity 100%) in all patients. SLNs were retrieved in all of patients intraoperatively (100% retrieval rate) with positive nodes found in 20% of patients. Tilmanocept also demonstrated 100% tissue specificity, with lymph nodal tissue confirmed histologically, with no false positives. CONCLUSION: Tilmanocept is a reliable radiotracer for assessing the nodal status in patients with CM and OCSCC. Our group is the first to evaluate the use of Tilmanocept in the Australian setting, adding to the limited studies worldwide.

Outcomes after definitive treatment for head and neck angiosarcoma.

INTRODUCTION: Head and neck angiosarcoma (HN-AS) is a rare and aggressive, representing <1% of all head and neck malignancies. It is characterized by a high rate of local recurrence and poor 5-year survival (10-54%). Australian data in this rare disease is lacking. We aim review the clinical outcomes of HN-AS from two high volume head and neck cancer units in Australia. METHODS: Retrospective chart review. RESULTS: A total 26 patients were identified, consist of predominantly male patients (81%) with a mean age of 77 year old. Most of the HN-AS arises from the scalp (62%). The 5-year overall survival (OS) and disease free survival (DFS) were 41% and 15%, respectively. Patients treated with upfront surgery with adjuvant therapy has better OS and DFS compared with patients receiving upfront chemoradiotherapy (median OS 3.63 vs. 0.53 years, P = 0.011 and median DFS 1.19 vs. 0.33 years, P = 0.001). There is no difference in OS or DFS for the sites of HN-AS or age of patients. Recurrences were noted in 15 patients (57.7%). For those with metastatic disease, the most common site was the lung (80%) with a median time to development of distant disease of 2.7 years (range 1.8-3.6 years). In patients who underwent salvage treatment, the median survival (post-salvage) was 1.3 years (0-2.8 years). CONCLUSION: This is the first Australian report of treatment patterns and outcomes of patients with HN-AS. Our cohort confirms that HN-AS is a slowly progressive disease with poor survival. Patients treated with surgery and adjuvant radiotherapy in this series had better outcomes compared with those treated with chemoradiotherapy alone. The role of neoadjuvant chemotherapy is an area of ongoing research.

Does Sentinel Lymph Node Biopsy Accurately Stage the Clinically Negative Neck in Early Oral Cavity Squamous Cell Carcinoma?

PURPOSE: Sentinel lymph node biopsy (SLNB) is being increasingly used worldwide as a minimally invasive option to stage the clinically node-negative neck (N0) in patients with early oral cavity squamous cell carcinomas (OCSCC). We performed this trial to assess the reliability and validity of the technique. METHODS: We did this prospective interventional nonrandomized study in patients with early (cT1-T2 OCSCC) and with negative neck. All patients underwent preoperative lymphoscintigraphy; SLNB was followed immediately by completion neck dissection (CND), thus each patient serving as their own control. The primary outcomes evaluated are sentinel lymph node (SLN) detection rate, SLN retrieval rate, and SLN status (positive or negative) compared with pathology of CND specimen to detect any false negatives. The secondary outcomes included SLN analyses (tumor burden, location in different levels of the neck, laterality, extracapsular spread, and total nodes positive) and overall survival. RESULTS: Of 60 patients, 59 (98%) had successful SLN detection with the lymphoscintigram failing to localize in 1 patient. Of the remaining 59 patients, 58 (96%) had all the SLNs retrieved, resulting in 96.4% sentinel node retrieval rate. In total, 24 (41%) SLNs were positive with 1 false negative. Using a combination of SLN and CND findings as the gold standard for lymph node involvement status, SLNB had a sensitivity of 96% (95% confidence interval [CI]: 80-100%), a specificity of 100% (95% CI: 90-100%), and negative predictive value of 97% (95% CI: 85-100%). CONCLUSION: The results of this study suggest that SLNB is an accurate technique to assess the nodal status in patients with cT1-T2 N0 OCSCC and should be considered for eligible patients.

Tumor depth of invasion versus tumor thickness in guiding regional nodal treatment in early oral tongue squamous cell carcinoma.

OBJECTIVES: Tumor thickness (TT) and tumor depth of invasion (DOI) correlate with the risk of regional lymph node metastases in early oral tongue squamous cell carcinoma (OTSCC). We aimed to determine optimal cutoff points to guide elective nodal treatment in early OTSCC. STUDY DESIGN: This retrospective study included 145 patients treated between 1995 and 2012 for histologically proven OTSCC (<4 cm). The minimum P value method was used to calculate the cut-point values of TT and DOI that predicted for nodal disease. The utility of the DOI cut-point value and the 5-mm DOI currently used for staging were then compared. RESULTS: Logistic regression analysis demonstrated that DOI (P = .00036) and TT (P = .0001) were highly correlated with nodal disease and each other. The cut-points that best predicted for nodal disease were 4.5 mm for DOI and 8 mm for TT. There was no difference in utility between DOIs of 4.5 mm and 5 mm. CONCLUSIONS: TT and DOI were highly correlated with nodal risk but had different cut-points for prediction. Our findings highlight the need to recognize these parameters as discrete entities and to report them appropriately. This study's findings support the use of the 5-mm DOI, currently used for staging, as also the threshold value to guide elective nodal treatment.

Education and support needs in patients with head and neck cancer: A multi-institutional survey.

BACKGROUND: Head and neck cancer (HNC) encompasses a diverse group of tumors, and thus providing appropriate and tailored information to patients before, during, and after treatment is a challenge. The objective of the current study was to characterize the experience and unmet needs of patients with HNC with regard to information and support provision. METHODS: A 28-question, cross-sectional survey was completed by patients treated for HNC at 1 of 4 institutions in New South Wales, Australia (Chris O'Brien Lifehouse and Liverpool, Westmead, and Wollongong hospitals). It consisted of the adapted Kessler Psychological Distress Scale and questions assessing information quality, quantity, and format. RESULTS: A total of 597 patients responded. The mean age of the patients was 58 years (range, 21-94 years) with 284 men and 313 women (1:1.1). The majority of patients reported information concerning the disease process (76%), prognosis (67%), and treatment (77%) was sufficient, and approximately 50% reporting having received little or no information regarding coping with stress and anxiety. A substantial percentage of patients reported receiving minimal information concerning psychosexual health (56%) or the availability of patient support groups (56%). The majority of patients preferred access to multiple modes of information delivery (72%), with the preferred modality being one-on-one meetings with a health educator (37%) followed by internet-based written information (19%). CONCLUSIONS: Patients with HNC are a diverse group, with complex educational and support needs. Patients appear to be given information regarding survivorship topics such as psychological well-being, patient support groups, and psychosexual health less frequently than information concerning disease and treatment. Verbal communication needs to be reinforced by accessible, well-constructed, written and multimedia resources appropriate to the patient's educational level. Cancer 2017;123:1949-1957. © 2017 American Cancer Society.

Sentinel lymph node biopsy for early oral cancers: Westmead Hospital experience.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become an alternative option to elective neck dissection (END) for early oral cavity squamous cell carcinoma (OCSCC) outside of Australia. We sought to assess the technical feasibility of SLNB and validate its accuracy against that of END in an Australian setting. METHODS: We performed a prospective cohort study consisting of 30 consecutive patients with cT1-2 N0 OCSCC referred to the Head and Neck Cancer Service, Westmead Hospital, Sydney, between 2011 and 2014. All patients underwent SLNB followed by immediate selective neck dissection (levels I-III). RESULTS: A total of 30 patients were diagnosed with an early clinically node-negative OCSCC (seven cT1 and 23 cT2), with the majority located on the oral tongue. A median of three (range: 1-14) sentinel nodes were identified on lymphoscintigraphy, and all sentinel nodes were successfully retrieved, with 50% having a pathologically positive sentinel node. No false-negative sentinel nodes were identified using selective neck dissection as the gold standard. The negative predictive value (NPV) of SLNB was 100%, with 40% having a sentinel node identified outside the field of planned neck dissection on lymphoscintigraphy. Of these, one patient had a positive sentinel node outside of the ipsilateral supraomohyoid neck dissection template. CONCLUSION: SLNB for early OCSCC is technically feasible in an Australian setting. It has a high NPV and can potentially identify at-risk lymphatic basins outside the traditional selective neck dissection levels even in well-lateralized lesions.

The Role of [18F]FDG-PET/CT in Predicting Malignant Transformation of Plexiform Neurofibromas in Neurofibromatosis-1.

Background. Malignant peripheral nerve sheath tumours (MPNSTs) are difficult to diagnose and treat and contribute to significant morbidity and mortality for patients with Neurofibromatosis-1 (NF-1). FDG-PET/CT is being increasingly used as an imaging modality to discriminate between benign and malignant plexiform neurofibromas. Objectives. To assess the value of FDG-PET/CT in differentiating between benign and malignant peripheral nerve lesions for patients with Neurofibromatosis-1. Methods. A systematic review of the literature was performed prior to application of stringent selection criteria. Ultimately 13 articles with 796 tumours were deemed eligible for inclusion into the review. Results. There was a significant difference between mean SUVmax of benign and malignant lesions (1.93 versus 7.48, resp.). Sensitivity ranged from 89 to 100% and specificity from 72 to 94%. ROC analysis was performed to maximise sensitivity and specificity of SUVmax cut-off; however no clear value was identified (range 3.1-6.1). Significant overlap was found between the SUVmax of benign and malignant lesions making differentiation of lesions difficult. Many of the studies suffered from having a small cohort and from not providing histological data on all lesions which underwent FDG-PET/CT. Conclusion. This systematic review is able to demonstrate that FDG-PET/CT is a useful noninvasive test for discriminating between benign and malignant lesions but has limitations and requires further prospective trials.

A rare case of ameloblastic carcinoma.

Ameloblastic carcinoma is a rare type of ameloblastoma that has received little mention in the literature. While a number of cases have been published over many years, no institution has been able to produce a substantial case series. Ameloblastic carcinoma originates in the embryonic tooth components. It is believed to be an aggressive tumor that can metastasize; once metastasis occurs, the prognosis tends to be poor. Ameloblastic carcinoma is primarily a surgical condition that is best treated with resection; there has been little indication that other modalities are helpful. We present the case of a 40-year-old woman who was found to have a mandibular lesion by a dentist. After surgical resection, the tumor was found to be an ameloblastic carcinoma. The patient recovered without complication, and she was recurrence-free 18 months postoperatively. We also briefly review the available literature on the natural history of and management options for this rare tumor.