Takeichiro Aso

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.

Background 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). Materials and Methods 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. Results 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. Conclusions 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.

Utility of algorithm-based chemoradioselection in the treatment for advanced hypopharyngeal carcinoma.

Current organ‐preserving dose‐intensified modalities have apparently reached the limit of human tolerance. To optimize the therapeutic ratio, we evaluated the utility of a chemoradioselection strategy for the treatment of advanced hypopharyngeal carcinoma.

Prognostic stratification of patients with nasopharyngeal carcinoma based on tumor immune microenvironment

Little is known about immune‐related prognostic factors in patients with nasopharyngeal carcinoma (NPC).

Mucoepidermoid carcinoma of the sublingual gland harboring a translocation of the MAML2 gene: A case report

Among tumors of the major salivary glands, tumors in the sublingual gland are rare. Although mucoepidermoid carcinoma (MEC) represents a histological type of salivary gland tumor, it is occasionally difficult to diagnose due to its histological variation. The present study reports a case of MEC harboring a mastermind-like transcriptional coactivator 2 (MAML2) gene translocation in the sublingual gland. A 76-year-old Japanese woman with a mass in the left submandibular region was referred to Kurume University Hospital (Kurume, Japan). Computed tomography scans revealed that the tumor was predominantly located in the sublingual gland, and tumor resection was performed. Histologically, the tumor was composed of cells that exhibited low-grade nuclear atypia and clear and/or granular eosinophilic cytoplasm, and that were proliferating in solid patterns. Periodic acid-Schiff and alcian blue staining revealed a small number of mucinous cells in the tumor. Immunohistochemically, the tumor cells were positive for p40 and p63. Fluorescence in situ hybridization (FISH) analysis revealed a MAML2 gene split. The definitive pathological diagnosis was low-grade MEC, as the case lacked any factors indicative of high-grade malignancy. To the best of our knowledge, this is the first report of MEC in the sublingual gland with MAML2 gene translocation confirmed by FISH.

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.

1013PINDUCTION OF CD44 VARIANT 9-EXPRESSING CANCER STEM CELLS ATTENUATES THE EFFICACY OF CHEMORADIOSELECTION AND WORSENS THE PROGNOSIS OF PATIENTS WITH ADVANCED HEAD AND NECK CANCER

ABSTRACT Aim: 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 chemoradioselection 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). Methods: 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. Results: 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 5 candidate factors (T, N, stage, response to CCRT, and CD44v9), CD44v9 positivity alone was significantly correlated with the poor prognosis (HR: 3.140, 95% CI: 1.230-8.017, p = 0.0167). Furthermore, the survival rate of the CD44v9-induced group was significantly (p = 0.04) worse than the CD44v9-non-induced group. Conclusions: CRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. The addition of an xCT (a coupling molecule of CD44v9) inhibitor (e.g., sulfasalazine) to chemoradioselection may provide a new approach for clinically feasible CSC-targeted therapy in HNSCC, improving the efficacy of chemoradioselection and consequent organ preservation and survival. Disclosure: All authors have declared no conflicts of interest.