Overall radiation treatment time and pretreatment hemoglobin level were significant predictors for loco-regional failure after definitive concurrent chemotherapy and IMRT for SCCHN.

Combining chemotherapy with radiotherapy has improved the cure rate among patients with cancers of the cervix. Although one-half to two-thirds of the patients can be cured by radiation alone, such patients cannot be identified at present and must therefore suffer the burden of chemotherapy. Our long-range goal is to identify those cervical cancers that are radiosensitive and could be cured by radiotherapy alone. The advent of methods that permit the simultaneous analysis of expression patterns of thousands of genes, make it feasible to attempt to identify the molecular events related to radiosensitivity and the associated regulatory pathways. We hypothesize that the sensitivity of tumor cells to ionizing radiation (IR) is determined by the level of expression of specific genes that may be identified with the aid of cDNA microarrays. As the first step in testing this hypothesis, we determined the gene expression differences between two cell lines exhibiting different degrees of radiosensitivity. These were derived from the same tumor prior to treatment from a patient with squamous cell carcinoma of the cervix. The mRNA from these cells was subjected to cDNA analysis on a microarray of 5,776 known genes and ESTs. The expression of 52 genes of the total of 5,776 was elevated (maximum 4.1 fold) in the radioresistant cells as compared to the radiosensitive cells. Ten of the 52 sequences are known genes while 42 are ESTs. Conversely, the expression of 18 genes was elevated in the sensitive cells as compared to the resistant cells. Seven of these 18 are known genes while eleven are ESTs. Among the genes expressed differentially between the resistant and sensitive cells were several known to be associated with response to IR and many more genes and ESTs that had not previously been reported to be related to radiosensitivity. The genes that showed the greatest overexpression in the radioresistant cell line were metal-regulatory transcription factor-1, cytochrome P450 CYP1B1, adenomatosis polyposis coli, translation elongation factor-1, cytochrome-c oxidase, whereas in the sensitive cell line, transcription factor NF-kappa-B, metalloproteinase inhibitor-1 precursor, superoxide dismutase-2, insulin-like growth factor binding protein-3, guanine nucleotide-binding protein and transforming growth factor beta-induced protein were overexpressed.

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Background This study was carried out to determine if markers of nutritional status predict for locoregional failure following intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN). Methods We performed a retrospective chart review of 78 patients with SCCHN who received definitive CCRT. We compared patient factors, tumor characteristics, and nutritional status indicators between patients with and without locoregional failure. Results Fifteen of 78 patients (19%) experienced locoregional failure. Median follow-up for live patients was 38 months. On univariate analysis, pretreatment percentage of ideal body weight (%IBW) (p < .01), pretreatment hemoglobin (p = .04), and treatment duration (p < .01) were significant predictors of failure. On multivariate analysis, pretreatment %IBW (p = .04) and treatment time (p < .01) remained statistically significant. Conclusions Although treatment time is an accepted risk factor for failure, differences in outcome for patients with head and neck cancer undergoing definitive CCRT based on pre-treatment %IBW should be examined further.