Establishing Relevant ADC-based Texture Analysis Metrics for Quantifying Early Treatment-Induced Changes in Head and Neck Squamous Cell Carcinomas

Purpose: The purpose of this study is to identify which texture analysis metrics calculated from apparent diffusion coefficient (ADC) maps from patients with head and neck squamous cell carcinomas (HNSCC) provide quantifiable measures of tumor physiology changes. We discerned which imaging metrics were relevant using baseline agreement and variations during early treatment. Methods: For selective patients with stages II-IV HNSCC, ADC maps were generated from two baselines, taken 1 week apart, and one early treatment scan, obtained during the 2nd week of curative-intent chemoradiation therapy. Regions of interest (ROI), consisting of primary and nodal disease were drawn onto resampled ADC maps. Four 3D texture matrices describing local and regional relationships between voxel intensities in the ROIs were generated. From these, 38 texture metrics and 7 histogram features were calculated for each patient, including the mean and median ADC. Agreement between the two baseline measures was estimated with the intra-class correlation coefficient (ICC). For each metric with an ICC≥0.80, the Wilcoxon signed-rank test was used to test if the difference between the mean of the baselines and the early treatment was non-zero. Results: Texture analysis was implemented on nine patients that had both baselines and early treatment images. Due to baseline agreement, only 9 of the 45 metrics had an ICC ≥0.80, including ADC mean and median. Six of these 9 metrics had a p-value \u3c 0.05. Only 1 of the 9 metrics remained of interest, after applying the Holm correction to the alpha levels: the run length non-uniformity metric (p = 0.004) in the Gray Level Run Length Matrix. Conclusion: The feasibility of texture analysis is dependent on the baseline agreement of each metric, which disqualifies many texture characteristics. However, metrics with high ICC have potential to provide additional quantitative information for the assessment of early treatment changes for HNSCC

Prevention of radiochemotherapy-induced toxicity with amifostine in patients with malignant orbital tumors involving the lacrimal gland: a pilot study

BACKGROUND: To use amifostine concurrently with radiochemotherapy (CT-RT) or radiotherapy (RT) alone in order to prevent dry eye syndrome in patients with malignancies located in the fronto-orbital region. METHODS: Five patients (2 males, 3 females) with diagnosed malignancies (Non-Hodgkin B-cell Lymphoma, neuroendocrine carcinoma) involving the lacrimal gland, in which either combined CT-RT or local RT were indicated, were prophylactically treated with amifostine (500 mg sc). Single RT fraction dose, total dose and treatment duration were individually adjusted to the patient's need. Acute and late adverse effects were recorded using the RTOG score. Subjective and objective dry eye assessment was performed for the post-treatment control of lacrimal gland function. RESULTS: All patients have completed CT-RT or RT as indicated. The median total duration of RT was 29 days (range, 23 - 39 days) and the median total RT dose was 40 Gy (range, 36 - 60 Gy). Median lacrimal gland exposure was 35.9 Gy (range, 16.8 - 42.6 Gy). Very good partial or complete tumor remission was achieved in all patients. The treatment was well tolerated without major toxic reactions. Post-treatment control did not reveal in any patient either subjective or objective signs of a dry eye syndrome. CONCLUSION: The addition of amifostine to RT/CT-RT of patients with tumors localized in orbital region was found to be associated with absence of dry eye syndrome

Transoral resection of pharyngeal cancer: Summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6–7, 2011, Arlington, Virginia

Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6–7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)–initiated oropharyngeal cancers, and in those with HPV‐unrelated disease. The proceedings of this meeting are summarized. © 2012 Wiley Periodicals, Inc. Head Neck, 2012Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94490/1/23136_ftp.pd

The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma

BACKGROUND: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial. METHODS: Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy. Immunohistochemistry for HIF-1α, CAIX and GLUT1 was performed on tissue microarrays and assessed by two scorers (one pathologist). Prognostic analysis of disease-free survival (DFS) used Kaplan-Meier and Cox regression. RESULTS: Biobank and outcome data were available for 203 out of 216 randomised patients. High CAIX expression was associated with worse DFS (hazard ratio 2.28, 95% confidence interval: 1.44-3.59, P<0.001). Hypoxia-inducible factor-1α and GLUT1 were not prognostic. Carbonic anhydrase IX remained prognostic in multivariable analysis. CONCLUSIONS: The VorteX-Biobank contains tissue with linked outcome data and is an important resource for research. This study confirms hypoxia is linked to poor prognosis in STS and suggests that CAIX may be the best known marker. However, overlap between single marker positivity was poor and future work will develop an STS hypoxia gene signature to account for tumour heterogeneity

Classifying the evolutionary and ecological features of neoplasms

The consensus conference was supported by Wellcome Genome Campus Advanced Courses and Scientific Conferences. C.C.M. is supported in part by US NIH grants P01 CA91955, R01 CA149566, R01 CA170595, R01 CA185138 and R01 CA140657 as well as CDMRP Breast Cancer Research Program Award BC132057. M.J. is supported by NIH grant K99CA201606. K.S.A. is supported by NCI 5R21 CA196460. K. Polyak is supported by R35 CA197623, U01 CA195469, U54 CA193461, and the Breast Cancer Research Foundation. K.J.P. is supported by NIH grants CA143803, CA163124, CA093900 and CA143055. D.P. is supported by the European Research Council (ERC-617457- PHYLOCANCER), the Spanish Ministry of Economy and Competitiveness (BFU2015-63774-P) and the Education, Culture and University Development Department of the Galician Government. K.S.A. is supported in part by the Breast Cancer Research Foundation and NCI R21CA196460. C.S. is supported by the Royal Society, Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169), NovoNordisk Foundation (ID 16584), the Breast Cancer Research Foundation (BCRF), the European Research Council (THESEUS) and Marie Curie Network PloidyNet. T.A.G. is a Cancer Research UK fellow and a Wellcome Trust funded Investigator. E.S.H. is supported by R01 CA185138-01 and W81XWH-14-1-0473. M.Gerlinger is supported by Cancer Research UK and The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. M.Ge., M.Gr., Y.Y., and A.So. were also supported in part by the Wellcome Trust [105104/Z/14/Z]. J.D.S. holds the Edward B. Clark, MD Chair in Pediatric Research, and is supported by the Primary Children's Hospital (PCH) Pediatric Cancer Research Program, funded by the Intermountain Healthcare Foundation and the PCH Foundation. A.S. is supported by the Chris Rokos Fellowship in Evolution and Cancer. Y.Y. is a Cancer Research UK fellow and supported by The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. E.S.H. was supported in part by PCORI grants 1505–30497 and 1503–29572, NIH grants R01 CA185138, T32 CA093245, and U10 CA180857, CDMRP Breast Cancer Research Program Award BC132057, a CRUK Grand Challenge grant, and the Breast Cancer Research Foundation. A.R.A.A. was funded in part by NIH grant U01CA151924. A.R.A.A., R.G. and J.S.B. were funded in part by NIH grant U54CA193489

How should we measure and report radiotherapy-induced xerostomia?

Xerostomia is commonly measured and graded using objective measures of major salivary gland output and observer-rated toxicity grading. The separation between the different grades is somewhat ambiguous in the current toxicity grading systems. We propose a new grading system based primarily on the functional deficits associated with xerostomia. Salivary flow rates have been added as a criterion to the grading system, notwithstanding the weak correlation reported in most studies between the symptoms and objective functional measures. In addition to the observer-rated toxicity grading, recording of patient-reported quality of life, using validated instruments, is encourage