Induction of CD44 variant 9-expressing cancer stem cells might attenuate the efficacy of chemoradioselection and Worsens the prognosis of patients with advanced head and neck cancer.

At our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30-40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chmoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC).Through a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies.The intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9 positivity (HR: 3.145, 95% CI: 1.235-8.008, P = 0.0163) was significantly correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95% CI: 1.054-9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9-induced group was significantly (P = 0.04) worse than the CD44v9-non-induced group.CCRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy to enhance the efficacy of chemoradioselection and consequent organ preservation and survival

Treatment Outcomes of Locally Advanced Squamous Cell Carcinoma of the Ethmoid Sinus Treated with Anterior Craniofacial Resection or Chemoradiotherapy

We retrospectively analyzed 14 patients with locally advanced squamous cell carcinoma of ethmoid sinus (LASCC-ES) for the feasibility of anterior craniofacial resection (ACFR). Ethmoid cancer treatment comprised alternating chemoradiotherapy (ALCRT; n = 1), concomitant radiotherapy and intra-arterial cisplatin (RADPLAT; n = 4) and ACFR (n = 9). The 3- and 5-year overall survival (OS) rates of patients were 47.6 and 39.6%, respectively. The 3-year local control (LC) rates of chemoradiotherapy (CRT; ALCRT and RADPLAT) (n = 5) and ACFR (n = 9) groups were 0 and 66.7% (p = 0.012), respectively. The 3-year progression-free survival (PFS) rate of the CRT and ACFR groups were 0 and 55.6% (p = 0.018), respectively. The 3-year OS rate of the CRT and ACFR groups were 0 and 76.2% (p = 0.005), respectively. Postoperative pathological examinations confirmed positive margins in 3 (33%) of 9 cases. The 3-year LC and PFS rates of cases (n = 3) with positive surgical margins were significantly poorer than those of cases (n = 6) with negative surgical margins. Although ACFR for LASCC-ES is a feasible treatment, cases with positive surgical margins were more prone to local relapse. Therefore, surgical safety margins should be thoroughly assessed

(A) Disease specific survival curves based on the CD44 v9 positivity of surgically removed samples obtained from 72 non-chemoradioselected (N-CRS) patients.

<p>(B) Diseasespecific survival curves of 30 N-CRS patients who had paired biopsy and surgically removed samples. The patients were divided into 2 groups according to their levels of CD44v9 expression before and after concurrent chemoradiotherapy.</p

(A) Disease specific survival curves of all patients (n = 102) according to the chemoradioselection.

<p>(B) Disease specific survival curves based on the CD44 v9 positivity of biopsy samples (n = 60) obtained from 30 chemoradioselected (CRS) patients and 30 non-chemoradioselected (N-CRS) patients. (C) Disease specific survival curves based on the CD44 v9 positivity of biopsy samples obtained from 30 N-CRS patients.</p

Representative pictures of anti-CD44v9-antibody immunostaining.

<p>The staining intensity obtained in the basal cells of normal epithelium was used as a control (A). Tumor samples demonstrated strong (B), moderate (C), and weak (D) intensities relative to the control (A). Respective positive (E) and negative <u>(F</u>) stainings. Bar indicates 200 um.</p

Patient characteristics (<i>N</i> = 102).

<p>Patient characteristics (<i>N</i> = 102).</p