Quantitative lymph node burden as a 'very-high-risk' factor identifying head and neck cancer patients benefiting from postoperative chemoradiation.

Background: Adjuvant chemoradiation (CRT) is standard for head and neck squamous cell carcinoma (HNSCC) patients with positive margins or extranodal extension (ENE) following surgery. However, emerging evidence suggests the number of positive lymph nodes (LNs) is the dominant determinant of survival in non-oropharyngeal HNSCC and thus may better identify those benefiting from treatment intensification. Patients and methods: Patients from the National Cancer Database diagnosed with non-oropharyngeal HNSCC (oral cavity, larynx, hypopharynx) between 2004 and 2014 and undergoing surgical resection, neck dissection, and postoperative radiotherapy (RT) were included. Multivariable regression with first-order interaction terms was used to model the interaction between postoperative CRT and continuous number of positive LNs with respect to overall survival. Results: In total, 7144 patients met inclusion criteria. In multivariable analysis, increasing number of positive LNs was associated with both increasing mortality (P < 0.001) and increasing benefit from postoperative CRT versus RT alone (interaction P < 0.001). While there was no benefit from postoperative CRT in patients with 0-2 LN+ [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.86-1.07, P = 0.47], increased benefit was seen in those with 3-5 LN+ (HR 0.84, 95% CI 0.70-1.00, P = 0.05) and those with ≥6 LN+ (HR 0.65, 95% CI 0.51-0.82, P < 0.001) in multivariable models. By contrast, margin status and ENE did not reliably identify patients benefitting from postoperative CRT based on statistical tests of interaction. Even in patients with ENE, positive margins, or both, only those with ≥6 LN+ had improved survival with postoperative CRT. Conclusion: Increasing metastatic nodal burden was associated with increased benefit from CRT compared with RT alone, surpassing conventional high-risk factors in identifying patients benefiting from CRT. Stratification by metastatic LN number may characterize a very-high-risk patient cohort best suited for treatment intensification.

An examination of the elastic properties of tissue-mimicking phantoms using vibro-acoustography and a muscle motor system.

Tissue hardness, often quantified in terms of elasticity, is an important differentiating criterion for pathological identity and is extensively used by surgeons for tumor localization. Delineation of malignant regions from benign regions is typically performed by visual inspection and palpation. Although practical, this method is highly subjective and does not provide quantitative metrics. We have previously reported on Vibro-Acoustography (VA) for tumor delineation. VA is unique in that it uses the specific, non-linear properties of tumor tissue in response to an amplitude modulated ultrasound beam to generate spatially resolved, high contrast maps of tissue. Although the lateral and axial resolutions (sub-millimeter and sub-centimeter, respectively) of VA have been extensively characterized, the relationship between static stiffness assessment (palpation) and dynamic stiffness characterization (VA) has not been explicitly established. Here we perform a correlative exploration of the static and dynamic properties of tissue-mimicking phantoms, specifically elasticity, using VA and a muscle motor system. Muscle motor systems, commonly used to probe the mechanical properties of materials, provide absolute, quantitative point measurements of the elastic modulus, analogous to Young's modulus, of a target. For phantoms of varying percent-by-weight concentrations, parallel VA and muscle motor studies conducted on 18 phantoms reveal a negative correlation (p < - 0.85) between mean signal amplitude levels observed with VA and calculated elastic modulus values from force vs. indentation depth curves. Comparison of these elasticity measurements may provide additional information to improve tissue modeling, system characterization, as well as offer valuable insights for in vivo applications, specifically surgical extirpation of tumors.

Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient Kit(W-sh)/Kit(W-sh) sash mice.

BACKGROUND: Mast cell-deficient Kit(W)/Kit(W-v) mice are an important resource for studying mast cell functions in vivo. However, because they are compound heterozygotes in a mixed genetic background and are infertile, they cannot be crossed easily with other mice. OBJECTIVE: To overcome this limitation, we explored the use of Kit(W-sh)/Kit(W-sh) mice for studying mast cell biology in vivo. RESULTS: These mice are in a C57BL/6 background, are fertile and can be bred directly with other genetically modified mice. Ten-week-old Kit(W-sh)/Kit(W-sh) are profoundly mast cell-deficient. No mast cells are detected in any major organ, including the lung. Gene microarrays detect differential expression of just seven of 16,463 genes in lungs of Kit(W-sh)/Kit(W-sh) mice compared with wild-type mice, indicating that resting mast cells regulate expression of a small set of genes in the normal lung. Injecting 10(7) bone marrow-derived mast cells (BMMC) into tail veins of Kit(W-sh)/Kit(W-sh) mice reconstitutes mast cell populations in lung, stomach, liver, inguinal lymph nodes, and spleen, but not in the tongue, trachea or skin. Injection of BMMC into ear dermis or peritoneum reconstitutes mast cells locally in these tissues. When splenectomized Kit(W-sh)/Kit(W-sh) mice are intravenously injected with BMMC, mast cells circulate longer and are found more often in the liver and inguinal lymph nodes, indicating that the spleen acts as a reservoir for mast cells following injection and limits migration to some tissues. CONCLUSION: In summary, these findings show that mast cell-deficient Kit(W-sh)/Kit(W-sh) mice possess unique attributes that favour their use for studying mast cell functions in vivo.