Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have poor efficacy in head and neck squamous cell carcinoma (HNSCC). Because the insulin-like growth factor-1 receptor (IGF1R) generates potent prosurvival signals and has been implicated in therapeutic resistance, its ability to induce resistance to EGFR-TKIs was studied in vitro. Five HNSCC cell lines demonstrated reduced sensitivity to the EGFR-TKI gefitinib when the IGF1R was activated. In SCC-25 and Cal27 cells, gefitinib inhibited basal and EGF-stimulated EGFR, Erk and Akt phosphorylation and reduced cell number. This correlated with initiation of apoptosis based on a 4-fold increase poly-(ADP-ribose) polymerase (PARP) cleavage and a 2.5-fold increase in Annexin V positivity. The apoptotic response and reduction in cell number were blocked by IGF1R activation, which resulted in phosphorylation of both Erk and Akt. In both cell lines, IGF1R-induced Erk but not Akt activation was eliminated by gefitinib. IGF1R-induced gefitinib resistance was unaffected by MEK inhibition with U0126, but was partially impaired by inhibition of phosphatidylinositol 3′-kinase (PI3K) with LY294002. The IGF1R-TKI PQ401 inhibited growth of SCC-25 and Cal27 cells alone and also acted synergistically with gefitinib. Thus the IGF1R can make HNSCC cells resistant to EGFR-TKI treatment via a prosurvival mechanism. Of 8 studied, all HNSCC tumor samples expressed the IGF1R and 5 demonstrated detectable IGF1R phosphorylation, suggesting that this receptor may be relevant in vivo, and thus combined EGFR/IGF1R inhibition may be necessary in some patients for effective targeted molecular therapy.

2b Laryngoscope, 126:1567-1571, 2016.

Patients who receive ≥ 3 units of blood after free tissue transfer for HNC had a significantly increased risk of death after controlling for age, preoperative hemoglobin and albumin, cancer stage, and adverse pathologic features. Increased transfusions are also associated with higher wound infection rates. The increased tendency to transfuse free flap patients in order to maintain a threshold hematocrit may have a detrimental impact on survival and wound infections and should be revisited.

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In addition to defect location and extent, availability of surrounding tissue and wound healing characteristics direct reconstruction. Patients who receive radiation therapy are at increased risk of complications. Use of vascularized tissue is critical for successful management, making local flaps and free tissue transfer the mainstay of reconstruction.