Future of the TNM classification and staging system in head and neck cancer

Staging systems for cancer, including the most universally used TNM classification system, have been based almost exclusively on anatomic information. However, the question arises whether staging systems should be based on this information alone. Other parameters have been identified that should be considered for inclusion in classification systems like the TNM. This is all the more important, as a shift toward nonsurgical treatments for head and neck cancer has been made over the years. For these treatment modalities tumor/biologic characteristics next to anatomic information may be particularly important for treatment choice and outcome. The shortcomings of the current TNM classification system will be discussed, along with suggestions for improvement and expansion of the TNM system based on tumor, patient, and environment‐related factors. Further improvement of the TNM classification is expected to result in better treatment choices, outcome and prognostication of patients with head and neck cancer. © 2010 Wiley Periodicals, Inc. Head Neck, 2010     

The role of postoperative chemoradiation for oropharynx carcinoma: A critical appraisal of the published literature and National Comprehensive Cancer Network guidelines

The National Comprehensive Cancer Network (NCCN) describes the presence of extracapsular spread and/or positive margins in oropharynx cancer (OPC) as an indication for the addition of chemotherapy to postoperative radiation. The guideline's category 1 consensus is based on what they term high‐level evidence. For this study, the authors performed a critical appraisal of the research upon which the NCCN guideline is based and assessed its relevance in the era of human papillomavirus (HPV)/p16‐positive OPC. Multiple shortcomings were identified, including patient exclusion after randomization and the use of unplanned subgroup analyses without multivariate adjustment, which undermined internal validity. Indeterminate HPV/p16 status limited external validity. Given the unique biology of HPV/p16‐positive tumors and the problems of internal and external validity, the authors concluded that the literature upon which the recommendation for the addition of chemotherapy to adjuvant radiation was based does not generate high‐level evidence, and its relevance for the postoperative management of patients with HPV/p16‐positive OPC remains unknown. Cancer 2015;121:1747–1754. © 2015 American Cancer Society.     

Proceedings From FDA/A.S.P.E.N. Public Workshop

The development of intravenous fat emulsion (IVFE) is the culmination of physiological, biochemical, nutritional, and medical scientific advancements. IVFEs have the ability to deliver critical nutritional substrates to the patient. Recent literature purports that they may also play roles in modulation of immune functionality and pulmonary physiology, but data supporting these potential benefits are limited. While soybean‐based IVFEs have comprised the dominant fat in U.S. markets, a number of other novel IVFEs may prove to optimize the care of children and adults in both hospitalized and home settings. The October 2013 U.S. Food and Drug Administration (FDA)/American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Public Workshop brought together scientists, researchers, and clinical experts to present updated clinical perspectives of IVFEs, including historical development, current state of usage throughout the world, and considerations for the regulatory approval of new IVFEs in the United States.     

Pediatric Intestinal Failure–Associated Liver Disease: Challenges in Identifying Clinically Relevant Biomarkers

Background: Intestinal failure–associated liver disease (IFALD) is complex and diagnosed by concurrent use of parenteral nutrition, clinical presentation, and alterations in hepatic biomarkers exclusive of other causes of liver disease. In comparison with individual measures, composite biomarkers may provide a more effective means for assessing disease progression and response to treatment than single parameters. Since IFALD is considered by some to be a type of drug‐induced liver injury (DILI), those diagnostic criteria could potentially be used in this population. Using a preexisting database of children treated for IFALD, our aim was to determine if a similar composite biomarker could be applied to this population. Study Design: Adult DILI criteria were applied at baseline, when treatment for IFALD (ie, direct bilirubin ≥2.0 mg/dL) was initiated. Results: A total of 214 patients with IFALD treated at Boston Children’s Hospital were identified; 168 patients were eligible for analysis. Most patients analyzed were male (61%) and preterm (87%). Alkaline phosphatase (ALP) ≥2× upper limit of normal (ULN) captured the least amount of DILI (11%), while γ‐glutamyltransferase (GGT) ≥1× ULN accounted for the most (62%). Using adult DILI criteria, 60 (39%) patients with IFALD were found to have DILI. Substituting GGT ≥1× ULN for ALP ≥2× ULN improved the sensitivity, with 105 (69%) of patients meeting at least 1 criterion for DILI. Conclusion: Numerous challenges made it difficult to apply the DILI criteria to children with IFALD. Direct bilirubin, fractionated ALP, and perhaps GGT may be more suitable. Given its complex etiology and the age‐based differences due to hepatic immaturity and growth, a more suitable composite marker needs to be developed to assess IFALD in this population.