Luuk M. Janssen

Diffusion-weighted MR Imaging in Laryngeal and Hypopharyngeal Carcinoma: Association between Apparent Diffusion Coefficient and Histologic Findings

PURPOSE To investigate the relationship between the histologic characteristics of head and neck squamous cell carcinoma and apparent diffusion coefficient (ADC) at diffusion-weighted magnetic resonance (MR) imaging. MATERIALS AND METHODS The institutional ethics committee approved this study and waived informed consent. In head and neck squamous cell carcinoma, local failure after chemotherapy and/or radiation therapy correlates with pretreatment ADC. However, the histopathologic basis of this correlation remains unclear. In this study, 16 patients with head and neck squamous cell carcinoma were enrolled (median age, 60 years; range, 49-78 years). Before undergoing total laryngectomy, patients underwent 1.5-T diffusion-weighted MR imaging. After resection, whole-mount hematoxylin-eosin-stained sections were registered to the MR images. Cellular density; nuclear, cytoplasmic, and stromal area; and nuclear-cytoplasmic ratio within the tumor were calculated by using image-based segmentation on four consecutive slices. Mean ADC of the corresponding tumor region was calculated. Spearman correlations between ADC and histologic characteristics were calculated. RESULTS ADC was significantly and inversely correlated with cell density (n = 16, r = -0.57, P = .02), nuclear area (n = 12, r = -0.64, P = .03), and nuclear-cytoplasmic ratio (n = 12, r = -0.77, P ≤ .01). ADC was significantly and positively correlated with percentage area of stroma (n = 12, r = 0.69, P = .01). Additionally, the percentage area of stroma was strongly interdependent with the percentage area of nuclei (n = 12, r = -0.97, P ≤ .01). CONCLUSION ADC was significantly correlated with cellularity, stromal component, and nuclear-cytoplasmic ratio. The positive correlation of ADC and stromal component suggests that the poor prognostic value of high pretreatment ADC might partly be attributed to the tumor-stroma component, a known predictor of local failure.

Diffusion-weighted imaging in head and neck squamous cell carcinomas: A systematic review

The purpose of this study was for us to review diagnostic accuracy of diffusion‐weighted imaging (DWI) in primary head and neck squamous cell carcinomas (HNSCCs), detection of metastatic lymph nodes, and recurrences.

Correlation of human papillomavirus status with apparent diffusion coefficient of diffusion-weighted MRI in head and neck squamous cell carcinomas

Identification of prognostic patient characteristics in head and neck squamous cell carcinoma (HNSCC) is of great importance. Human papillomavirus (HPV)‐positive HNSCCs have favorable response to (chemo)radiotherapy. Apparent diffusion coefficient, derived from diffusion‐weighted MRI, has also shown to predict treatment response. The purpose of this study was to evaluate the correlation between HPV status and apparent diffusion coefficient.

The effect of exercise therapy in head and neck cancer patients in the treatment of radiotherapy-induced trismus: A systematic review.

Trismus is characterized by a reduced ability to open the mouth, directly affecting many aspects of daily life, such as chewing, swallowing, speaking and maintaining oral hygiene. Several studies have shown that trismus affects health related quality of life. Radiotherapy in the head and neck area is identified as one of the most frequent causes of trismus in head and neck cancer (HNC) patients. Currently, there is no standard treatment for trismus. Several stretching techniques and jaw mobilizing devices are available, but their effect in radiotherapy-induced trismus is still largely unknown. With this review we give an overview of the present relevant literature and compare the effect of exercise therapy versus no exercise therapy on jaw mobility, expressed in millimeters mouth opening, in HNC patients with radiotherapy-induced trismus. A systematic literature search in four electronic bibliographic databases was conducted in July 2014. Selected articles were critically appraised on relevance and validity. Best available evidence was analyzed and compared. Three of the four selected articles show a significant increase (p-value<0.05) in maximal interincisal opening (MIO) after exercise therapy using a jaw-mobilizing device. One article reports a significant decrease in MIO. However, this decrease is less in the intervention group, which implies a positive effect of exercise therapy. Based on this current best clinical evidence, it can be assumed that exercise therapy with a jaw-mobilizing device yields better results than no exercise, with regards to opening of the mouth in HNC patients with radiotherapy-induced trismus.

The accuracy of target delineation in laryngeal and hypopharyngeal cancer

Abstract Background and purpose. To determine the spatial correspondence between the gross tumor volume (GTV) delineated on computer tomography (CT) and the actual tumor on histopathology. Material and methods. Sixteen patients with T3 or T4 laryngeal or hypopharyngeal cancer underwent a CT scan before total laryngectomy. The GTV was delineated on CT by three independent observers and by consensus between the three observers. After surgery, whole-mount hematoxylin-eosin stained (H&E) sections were obtained. One pathologist delineated the tumor in the H&E sections (tumorH&E). The reconstructed specimen was registered to the CT scan in order to compare the GTV to the tumorH&E in three dimensions. The overlap between the GTV and the tumorH&E was calculated and the distance between the volumes was determined. Results. Tumor tissue was delineated in 203 of 516 H&E sections. For 14 patients a detailed analysis could be performed. The GTV volume was on average 1.7 times larger than the volume of the tumorH&E. The mean coverage of the tumorH&E by the consensus GTV was 88%. tumorH&E tissue was found at 1.6 mm to 12.9 mm distance outside the GTV depending on observer and patient. Conclusions. GTVs delineated on CT for laryngeal and hypopharyngeal cancer were 1.7 times larger than the tumor. Complete coverage of the tumor by the GTV was, however, not obtained.

Influence of tumor and microenvironment characteristics on diffusion-weighted imaging in oropharyngeal carcinoma : A pilot study

OBJECTIVES Diffusion weighted imaging (DWI) is a frequently performed MRI sequence in cancer patients. While previous studies have shown the clinical value of the apparent diffusion coefficient (ADC) for response prediction and response monitoring, less is known about the biological background of ADC. In the tumor microenvironment, hypoxia and increased proliferation of tumor cells contribute to resistance to (radio-)therapy, while high T-cell influx is related to better prognosis. We investigated the correlation between these three tissue characteristics and ADC in 20 oropharyngeal squamous cell carcinoma patients. MATERIALS AND METHODS 20 patients with oropharyngeal squamous cell carcinoma (OPSCC) who underwent 1.5 T MRI, including DWI were included in this pilot study. Corresponding formalin-fixed paraffin-embedded tumor tissues were immunohistochemically analyzed for protein expression of hypoxia-inducible factor 1a (HIF-1a), Ki-67 and CD3. Expression of these markers was correlated with ADC. RESULTS ADC negatively correlated with Ki-67 expression (p = .024) in tumor cells. There was a significant negative correlation between ADC and CD3-positive cell count (p = .009). No correlation was observed between HIF-1a expression and ADC. CONCLUSION This study suggests that ADC reflects characteristics of tumor cells as well as the surrounding microenvironment. Interestingly, high tumor proliferation (a negative prognostic factor) and high T-cell influx (a beneficial prognostic factor) are both associated with a lower ADC. Further studies should be performed to correlate ADC to these histological characteristics in relation to previously known factors that affect ADC, to gain further knowledge on the role of DW-MRI in diagnostics and personalized medicine.

Use of the 2‐μm continuous wave thulium laser for the resection of oral squamous cell carcinomas does not impair pathological assessment

Current resection modalities for oral squamous cell carcinomas (OSCC) vary from cold steel over CO2 laser to monopolar electro‐surgery (MO). We compared thulium laser (TL) as a new modality with MO with regards to pathological assessment.

Systematic review of the diagnostic value of magnetic resonance imaging for early glottic carcinoma

In early glottic cancer, accurate assessment of tumor extension, including depth infiltration, is of great importance for both staging, therapeutic approach and systematic comparison of data. Our goal was to assess the diagnostic value of MRI in pre‐therapeutic staging of primary early stage (T1 and T2) glottic carcinoma.

Influence of FDG-PET on primary nodal target volume definition for head and neck carcinomas

Abstract Background: The role of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in routine diagnostic staging remains controversial. In case of discordance between FDG-PET and CT, a compromise has to be made between the risk of false positive FDG-PET and the risk of delaying appropriate salvage intervention. Second, with intensity modulated radiation therapy (IMRT), smaller radiation fields allow tissue sparing, but could also lead to more marginal failures. Methods: We retrospectively studied 283 patients with head and neck carcinoma scheduled for radiotherapy between 2002 and 2010. We analyzed the influence of FDG-PET/CT versus CT alone on defining nodal target volume definition and evaluated its long-term clinical results. Second, the location of nodal recurrences was related to the radiation regional dose distribution. Results: In 92 patients, CT and FDG-PET, performed in mold, showed discordant results. In 33%, nodal staging was altered by FDG-PET. In 24%, FDG-PET also led to an alteration in nodal treatment, including a nodal upstage of 18% and downstage of 6%. In eight of these 92 patients, a regional recurrence occurred. Only two patients had a recurrence in the discordant node on FDG-PET and CT and both received a boost (high dose radiation). Conclusion: These results support the complementary value of FDG-PET/CT compared to CT alone in defining nodal target volume definition for radiotherapy of head and neck cancer.

OC-0068: Comparison of GTV delineations on CT, MRI and FDG-PET of laryngeal and hypopharyngeal carcinoma with histopathology

increasingly used for response monitoring and prediction. In this study the diagnostic potential of DCE-MRI for treatment response assessment in esophageal cancer is investigated. Materials and Methods: In 12 patients receiving nCRT, DCEMRI studies were performed before treatment (pre), after 813 fractions (per) and 5-7 weeks after completion of nCRT, prior to surgery (post). After resection pathologic assessment of the tumor regression grade (TRG) was performed following the Mandard score. For analysis a distinction was made between a group of good responders (GR), defined as pCr (TRG 1) or near-pCr (TRG 2), and poor responders (noGR) with TRG ≥ 3. The primary tumor was delineated on the T2W images before, during and after nCRT. This delineated volume was contracted with an isotropic margin of 2 mm to account for residual motion and partial volume effects. Within this contracted volume mean, median and 75 percentile (P75) of the AUC of the contrast agent concentration was calculated. Here, the AUC was defined as the integral over the concentration curve (60 seconds, starting at inflow of contrast agent). Results: In 4 patients (33%) pCR was found and a total of 5 patients (42%) showed a good response. Initial P75 AUC values were the same across GR and noGR. Relative changes in mean, median and P75 AUC between pre and per treatment were all found to be significant across the two groups, while the same parameters comparing pre and post treatment were not significant. All noGR showed an increase in AUC comparing relative changes between pre and per treatment (fig. A), while 80% of GR remained similar or decreased. The ΔP75 pre-per was found to be most predictive (-6%±29% for GR [mean ± SD] vs. 76%±58% for noGR, p=0.005) (fig B). With a cut-off value of 17.4% an area under the ROC curve of 0.97, sensitivity of 80%, specificity of 100%, positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 88% is found.