Organ preservation following radiation therapy and concurrent intra-arterial low dose cisplatin infusion for advanced T2 and T3 laryngeal cancer: Long-term clinical results from a pilot study.

BACKGROUND: This pilot study evaluated the long-term outcomes of patients with advanced T2 or T3 squamous cell carcinoma of the larynx (SCC-L) who were treated with selective intra-arterial cisplatin and concomitant radiotherapy (RADPLAT). METHODS: We retrospectively investigated the data of 49 patients with advanced T2 or T3 SCC-L who received a RADPLAT regimen with low-dose cisplatin. RESULTS: The 5-year locoregional control, disease-specific survival, and overall survival rates were 83.3%, 88.1%, and 82.6%, respectively, while the 5-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates were 89.6%, 79.4%, and 77.1%, respectively. The incidences of grade 3-4 hematologic and nonhematologic toxicities were 18% and 6%, respectively. Although two patients (4%) developed late toxicities within 5 years following RADPLAT, no other events were noted beyond 5 years. CONCLUSION: This pilot study demonstrated that RADPLAT is feasible and safe and yielded favorable survival outcomes and functional laryngeal preservation in patients with advanced T2 or T3 SCC-L. LEVEL OF EVIDENCE: 3.

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

BACKGROUND: Little is known about immune-related prognostic factors in patients with nasopharyngeal carcinoma (NPC). METHODS: We retrospectively reviewed 66 patients with NPC. Epstein-Barr virus (EBV) status, programmed cell death-ligand 1 (PD-L1) expression, and tumor-infiltrating lymphocyte (TIL) densities were analyzed, and a prognostic evaluation of these immune-related parameters was performed. RESULTS: The multivariate analyses demonstrated that CD8-positive TIL density but not PD-L1 expression on tumor cells or immune cells was a significant predictive factor for progression-free survival (PFS) and overall survival (OS). Subgroup analyses demonstrated that a positive PD-L1 expression on tumor cells in combination with a higher CD8-positive TIL density was significantly associated with favorable prognosis, whereas positive PD-L1 expression on tumor cells with lower CD8-positive TIL density was associated with worse prognosis. CONCLUSION: Our results suggest that PD-L1 expression on tumor cells in combination with CD8-positive TIL density could be a useful predictive biomarker for risk stratification in patients with NPC.

Treatment outcomes of locally advanced squamous cell carcinoma of the maxillary sinus treated with chemoradioselection using superselective intra-arterial cisplatin and concomitant radiation: Implications for prognostic factors.

BACKGROUND: This study clarified the clinical results of locally advanced squamous cell carcinoma of the maxillary sinus (SCC-MS) that was treated with chemoradioselection using superselective intra-arterial cisplatin and concomitant radiation (RADPLAT). Prognostic factors were also investigated. METHODS: We retrospectively analyzed 63 locally advanced SCC-MS patients treated with initial RADPLAT followed by sequential RADPLAT (S-RADPLAT) or surgery. RESULTS: The 5-year progression-free survival (PFS) and overall survival (OS) rates of patients with T3, T4a, or T4b disease were 72.2%, 46.6%, and 33.3% (p = 0.104) and 83.3%, 51.6%, and 33.3% (p = 0.031), respectively. The 5-year PFS and OS rates of the S-RADPLAT or surgery groups with T4 disease were 39.6% and 60.6% (p = 0.199) and 44.7% and 63.3% (p = 0.276), respectively. Tumor extension into the medial and/or lateral pterygoid muscle (p < 0.001) and N classification (p = 0.012) were considered significant factors for PFS. Regarding OS, tumor extension into the medial and/or lateral pterygoid muscle (p = 0.005) was considered a statistically significant risk factor. CONCLUSIONS: It may be better for T4 non-responders to initial RADPLAT to undergo surgery. Patients with high risk factors of positive neck metastasis or pterygoid muscle extension may need adjuvant chemotherapy.

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.

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.

BACKGROUND: 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. METHODS: Fifty-five patients with advanced hypopharyngeal carcinoma were enrolled in our algorithm-based protocol. After 40 Gy of concurrent chemoradiation therapy (CCRT), patients who were chemoradioselected (chemoradioselected group, complete response [CR] at the primary site) received further 30 Gy of CCRT up to 70 Gy, whereas the remaining nonchemoradioselected (nonchemoradioselected group) patients underwent radical surgery. RESULTS: Based on this algorithm, 27 patients were chemoradioselected and 28 nonchemoradioselected. The 5-year cumulative disease-specific and overall survival (OS) rates were 76% and 65%, respectively. The chemoradioselected group demonstrated favorable laryngoesophageal dysfunction-free survival (77% at 3 years). CONCLUSION: Although preliminary, our results indicate that algorithm-based chemoradioselection may provide a novel platform for improving the treatment of advanced hypopharyngeal carcinoma by providing the complete advantages of CCRT and radical surgical resection.