Senada Koljenović

EORTC Melanoma Group sentinel node protocol identifies high rate of submicrometastases according to Rotterdam Criteria

Sentinel node (SN) status is the most important prognostic factor for disease-free survival (DFS) and overall survival (OS) in stages I-II melanoma. We evaluated the positive sentinel node identification rate of the EORTC Melanoma Group (MG) protocol as well as its capacity to identify minimal tumour burden, according to the Rotterdam Criteria in 421 consecutive patients. Correlations between primary tumour characteristics and SN tumour burden were investigated. The same 2 pathologists worked up all SNs according to the EORTC MG protocol and tumour burden was scored according to the Rotterdam Criteria (<0.1 mm, 0.1-1.0 mm and >1.0 mm for the largest diameter of the largest metastasis in the SN). The positive SN detection rate was 28.7% with a false negative rate of 10.4% at a median Breslow thickness of 2.1 mm. The high positive identification rate of about 30% of the EORTC MG protocol has been confirmed in this study. The protocol is sensitive and identifies submicrometastases (<0.1 mm) in a high percentage (18%). The variables SN tumour load, non-SN (NSN) status and ulceration of the primary were independent prognostic factors for DFS and OS in the multivariate analysis. At a median follow-up time of 4.3 years patients with minimal tumour burden (<0.1 mm) had a 5 year OS rate of 91%, virtually identical to 90% for SN-negative patients. The NSN positivity rate of 0% in these patients indicates that they may be spared a completion lymph node dissection (CLND) and its morbidity.

Discrimination between oral cancer and healthy tissue based on water content determined by Raman spectroscopy.

Tumor-positive resection margins are a major problem in oral cancer surgery. High-wavenumber Raman spectroscopy is a reliable technique to determine the water content of tissues, which may contribute to differentiate between tumor and healthy tissue. The aim of this study was to examine the use of Raman spectroscopy to differentiate tumor from surrounding healthy tissue in oral squamous cell carcinoma. From 14 patients undergoing tongue resection for squamous cell carcinoma, the water content was determined at 170 locations on freshly excised tongue specimens using the Raman bands of the OH-stretching vibrations (3350-3550 cm(-1)) and of the CH-stretching vibrations (2910-2965 cm(-1)). The results were correlated with histopathological assessment of hematoxylin and eosin stained thin tissue sections obtained from the Raman measurement locations. The water content values from squamous cell carcinoma measurements were significantly higher than from surrounding healthy tissue (p-value < 0.0001). Tumor tissue could be detected with a sensitivity of 99% and a specificity of 92% using a cutoff water content value of 69%. Because the Raman measurements are fast and can be carried out on freshly excised tissue without any tissue preparation, this finding signifies an important step toward the development of an intraoperative tool for tumor resection guidance with the aim of enabling oncological radical surgery and improvement of patient outcome.

Resection margins in oral cancer surgery: Room for improvement

The purpose of this review was to identify publications on resection margins in oral cancer surgery and compare these with the results from 2 Dutch academic medical centers. Eight publications were considered relevant for this study, reporting 30% to 65% inadequate resection margins (ie, positive and close margins), compared to 85% in Dutch centers. However, clinical outcome in terms of overall survival and recurrence seemed comparable. The misleading difference is caused by lack of unanimous margin definition and differences in surgicopathological approaches. This prevents comparison between the centers. Data from Dutch centers showed that inadequate resection margins have a significantly negative effect on local recurrence, regional recurrence, distant metastasis, and overall survival. These results confirm the need for improvement in oral cancer surgery. We underline the need for consistent protocols and optimization of frozen section procedures. We comment on development of optical techniques for intraoperative assessment of resection margins.

Risk Factors for Positive Deep Pelvic Nodal Involvement in Patients with Palpable Groin Melanoma Metastases: Can the Extent of Surgery be Safely Minimized?

BackgroundPatients with palpable melanoma groin metastases have a poor prognosis. There is debate whether a combined superficial and deep groin dissection (CGD) is necessary or if superficial groin dissection (SGD) alone is sufficient.AimThe aim of this study was to analyze risk factors for deep pelvic nodal involvement in a retrospective, multicenter cohort of palpable groin melanoma metastases. This could aid in the development of an algorithm for selective surgery in the future.MethodsThis study related to 209 therapeutic CGDs from four tertiary centers in The Netherlands (1992–2013), selected based on complete preoperative imaging and pathology reports. Analyzed risk factors included baseline and primary tumor characteristics, total and positive number of inguinal nodes, inguinal lymph node ratio (LNR) and positive deep pelvic nodes on imaging (computed tomography [CT]xa0±xa0positron emission tomography [PET], or PETxa0−xa0low-dose CT).ResultsMedian age was 57xa0years, 54xa0% of patients were female, and median follow-up was 21xa0months (interquartile range [IQR] 11–46xa0months). Median Breslow thickness was 2.10xa0mm (IQR 1.40–3.40xa0mm), and 26xa0% of all primary melanomas were ulcerated. Positive deep pelvic nodes occurred in 35xa0% of CGDs. Significantly fewer inguinal nodes were positive in case of negative deep pelvic nodes (median 1 [IQR 1–2] vs. 3 [IQR 1–4] for positive deep pelvic nodes; pxa0<xa00.001), and LNR was significantly lower for negative versus positive deep pelvic nodes [median 0.15 (IQR 0.10–0.25) vs. 0.33 (IQR 0.14–0.54); pxa0<xa00.001]. A combination of negative imaging, low LNR, low number of positive inguinal nodes, and no extracapsular extension (ECE) could accurately predict the absence of pelvic nodal involvement in 84xa0% of patients.ConclusionsPatients with negative imaging, few positive inguinal nodes, no ECE, and low LNR have a low risk of positive deep pelvic nodes and may safely undergo SGD alone.

Raman spectroscopy for assessment of bone resection margins in mandibulectomy for oral cavity squamous cell carcinoma

OBJECTIVESnThe aim of this study was to investigate the potential of Raman spectroscopy for detection of oral cavity squamous cell carcinoma (OCSCC) in bone resection surfaces during mandibulectomy.nnnMATERIALS & METHODSnRaman mapping experiments were performed on fresh mandible resection specimens from patients treated with mandibulectomy for OCSCC. A tumour detection algorithm was created based on water concentration and the high-wavenumber range (2800xa0cm-1-3050xa0cm-1) of the Raman spectra.nnnRESULTSnTwenty-six exxa0vivo Raman mapping experiments were performed on 26 fresh mandible resection specimens obtained from 22 patients. The algorithm was applied on an independent test set and showed an accuracy of 95%, a sensitivity of 95%, and a specificity of 87%.nnnCONCLUSIONnThese results form the basis for further development of a Raman spectroscopy tool as an objective method for intraoperative assessment of bone resection margins.

A nation-wide epidemiological study on the risk of developing second malignancies in patients with different histological subtypes of nasopharyngeal carcinoma

OBJECTIVEnRisk assessment of second head/neck and Epstein Barr Virus (EBV)-related malignancies in patients with different nasopharyngeal carcinoma (NPC) subtypes.nnnMETHODSnThis is a cross-sectional study. Pathology records were retrieved from PALGA (a Dutch pathology registry database) between 1995 and 2013. Second primary malignancy (SPM) data was extracted from PALGA. Odds ratios (OR) for SPM in the head/neck, and the upper/lower airways were calculated using logistic regression. Pearson X(2)-test and Fishers exact test were used to assess the relationship between NPC (and EBV-status) with SPM. Standardized incidence rates (SIR) were calculated.nnnRESULTSnHistologically diagnosed NPC (keratinizing and undifferentiated and differentiated non-keratinizing subtypes) (n=1175) were identified. NPC patients have an increased risk of second head/neck malignancies (SIR 4.7 95% CI 3.3-6.5). Keratinizing NPCs have an OR of 1.947 (95% CI 1.362-2.782) for SPM, an OR of 4.026 (95% CI 2.308-7.023) for carcinomas of the upper/lower airways, an OR of 4.306 (95% CI 2.299-8.066) for head/neck malignancies, an OR of 5.289 (95% CI 2.740-10.211) for HNSCC with a SIR of 4.7 (95CI 3.3-6.5). Non-keratinizing NPCs also have an increased risk of head/neck malignancies with a SIR of 3.2 (95% CI 1.8-5.1), but less than keratinizing NPCs (p=<0.001). Positive EBV-status is not associated with (EBV-related) SPM.nnnCONCLUSIONnNPCs have a higher risk of SPM regardless of EBV status. SPM (especially HNSCC and malignancies of the upper aerodigestive tract) are more prevalent in keratinizing NPC compared to non-keratinizing NPC. Close clinical follow-up of NPC patients, with specific attention on SPM, is justified.

Differences in cancer gene copy number alterations between Epstein-Barr virus-positive and Epstein-Barr virus-negative nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) treatment is mainly based on clinical staging. We hypothesize that better understanding of the molecular heterogeneity of NPC can aid in better treatment decisions. Therefore, the purpose of this study was to present our exploration of cancer gene copy‐number alterations (CNAs) of Epstein‐Barr virus (EBV)‐positive and EBV‐negative NPC.