Treatment selection for tonsillar squamous cell carcinoma

AbstractBackgroundThe optimal treatment for tonsillar squamous cell carcinoma (SCC) remains controversial. The purpose of this study was to evaluate long-term treatment outcomes of patients with tonsillar SCC, in order to aid in appropriate treatment selection.MethodsWe conducted a retrospective chart review of 105 patients with curatively treated tonsillar SCC between January 1996 and December 2005. Forty-three patients (41.0%) underwent primary surgery with or without adjuvant therapy (primary surgery group), and 62 patients (59.0%) were treated with radiotherapy/chemoradiotherapy (RT/CRT, organ preservation group). Twenty patients (19%) received tumor tonsillectomy before definitive RT/CRT and were grouped into the organ preservation group.ResultsNo significant differences were observed between the primary surgery and organ preservation groups in terms of local control (p = 0.212), regional control (p = 0.684), distant metastasis (p = 0.627), 5-year disease-specific survival (DSS, p = 0.774), and overall survival rates (OS, p = 0.667). The rates of major complication (p = 0.216), long-term dependency on feeding tubes (p = 0.876), and tracheostomy (p = 0.401) were also similar. Advanced T classification (T3–4) was the only factor associated with significantly worse DSS (p = 0.007) and OS (p = 0.012). However, there was also no difference in final treatment outcomes in T3–4 patients regardless of whether they were treated with primary surgery or RT/CRT. In the organ preservation group, tumor tonsillectomy before RT/CRT did not improve local control (p = 0.520) or other treatment outcomes, including 5-year DSS (p = 0.707) and OS (p = 0.745).ConclusionBoth primary surgery and RT/CRT organ preservation are effective treatments for tonsillar SCC. Single modality treatment, either surgery or RT/CRT, can typically be provided for stage I–II diseases. Although RT/CRT organ preservation is used more frequently for stage III–IV tonsillar SCC in recent years, primary surgery combined with adjuvant therapy still achieves equivalent outcomes. Multidisciplinary pretreatment counseling and the facilities and personnel available are therefore important for decision-making. In addition, if RT/CRT organ preservation is selected as the primary treatment, tumor tonsillectomy is not indicated

Modified Weekly Cisplatin-Based Chemotherapy Is Acceptable in Postoperative Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer

Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT) has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC). We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT. Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed. Results. Median follow-up time was 30.0 (3.1–73.0) months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%). Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%). No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively. Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC

Ectopic Thyroid Papillary Carcinoma Presenting as Bilateral Neck Masses

Ectopic thyroid papillary carcinoma presenting as bilateral neck lymph nodes metastasis is very rare. We report a 42-year-old male with midline submental ectopic thyroid papillary carcinoma presenting as bilateral progressively growing neck masses for 3 months. A right neck mass excisional biopsy was carried out and the pathology revealed metastatic papillary carcinoma. Total thyroidectomy, submental “ectopic thyroid tissue” excision and bilateral neck dissection were then performed. No primary lesions were found in the thyroid gland. Therefore, the differential diagnosis of bilateral neck masses should include cervical metastasis of ectopic papillary carcinoma

Epstein-Barr Virus Transcription Activator Rta Upregulates Decoy Receptor 3 Expression by Binding to Its Promoter▿

Decoy receptor 3 (DcR3) is a soluble decoy receptor belonging to the tumor necrosis factor receptor superfamily that is overexpressed in various malignant tumor types. DcR3 has been implicated in tumor cell survival by inhibiting apoptosis and by interfering with immune surveillance. A previous study showed that DcR3 expression is associated with Epstein-Barr virus (EBV)-positive lymphomas but rarely with non-EBV-positive B-cell lymphomas, suggesting that the presence of EBV may affect DcR3 expression. Here, we demonstrated enhanced DcR3 expression upon EBV reactivation in P3HR1 cells and in EBV-infected 293 cells. This enhancement, however, could not be detected in 293 cells infected with EBV with BRLF1 deleted. We found that EBV transactivator, Rta, could upregulate DcR3 expression by direct binding to an Rta-responsive element (RRE) located in the DcR3 promoter region and that this RRE is important for Rta-mediated DcR3 expression. Overexpressing CREB-binding protein (CBP) further enhanced Rta-dependent DcR3 expression, suggesting Rta-dependent DcR3 transcription activity is mediated by CBP. Previously, Rta was shown to enhance phosphatidylinositol-3 kinase (PI3-K) activity. However, Rta-transduced PI 3-K activity plays a minor role in DcR3 expression. This is the first report to demonstrate that Rta upregulates a cellular gene by direct binding to an RRE

Management of base of tongue squamous cell carcinoma: Experience with 85 patients in Taipei Veterans General Hospital

Background: The optimal treatment of base of tongue squamous cell carcinoma (BOTSCC) remains controversial. To optimize treatment planning, this study analyzed the outcomes of patients with BOTSCC treated in Taipei Veterans General Hospital. Methods: Retrospective chart reviews were performed for 107 patients with BOTSCC from January 1990 to December 2004, and 85 patients were included, with a mean follow-up interval of 38 months. Patients were divided into surgical and radiotherapy/chemoradiation therapy (RT/CRT) groups. Potentially significant variables for survival were analyzed. Results: The 3-year overall survival (OS) and disease-free survival rates were 40% and 37.1%, respectively. No significant differences in the patient and disease characteristics between the surgical (n = 39) and RT/CRT groups (n = 46) were found. Advanced overall stage (p = 0.034), cervical lymph node metastasis (p = 0.007), and regional recurrence (p = 0.024) were poor prognostic factors for OS. In early-stage disease (Stages I and II), the 3-year OS was higher in the surgical group (68.6%) than in the RT/CRT group (37.5%), but the significance was only borderline (p = 0.071). There was no significant difference in the 3-year OS between the patients in the surgical and CT/CRT groups with advanced-stage disease. In the surgical group, lymphovascular permeation (p = 0.015) and soft-tissue involvement (p = 0.01), determined by pathologic examination, were poor prognostic factors for OS. Recurrence occurred in 35 patients (41.2%), with no significant difference in local, regional, or distant control between the surgical and RT/CRT groups. Conclusion: These findings emphasize the importance of neck disease control in the treatment of BOTSCC. Although currently, RT/CRT is used more frequently, surgery may still have a role in the treatment of early-stage disease. Both surgery with adjuvant therapy and RT/CRT produced equivalent survival rates in the treatment of advanced-stage disease, but the recurrence rate was unsatisfactory. A more effective treatment modality with less early and late toxicity is needed

Regulation of Membrane-Type 4 Matrix Metalloproteinase by SLUG Contributes to Hypoxia-Mediated Metastasis12

The hypoxic tumor environment has been shown to be critical to cancer metastasis through the promotion of angiogenesis, induction of epithelial-mesenchymal transition (EMT), and acquisition of invasive potential. However, the impact of hypoxia on the expression profile of the proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP) is a glycosyl-phosphatidyl inositol-anchored protease that has been shown to be overexpressed in human cancers. However, detailed mechanisms regarding the regulation and function of MT4-MMP expression in tumor cells remain unknown. Here, we demonstrate that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α) induced MT4-MMP expression in human cancer cells. Activation of SLUG, a transcriptional factor regulating the EMT process of human cancers, by HIF-1α was critical for the induction of MT4-MMP under hypoxia. SLUG regulated the transcription of MT4-MMP through direct binding to the E-box located in its proximal promoter. Short-interference RNA-mediated knockdown of MT4-MMP attenuated in vitro invasiveness and in vivo pulmonary colonization of tumor cells without affecting cell migratory ability. MT4-MMP promoted invasiveness and pulmonary colonization through modulation of the expression profile of MMPs and angiogenic factors. Finally, coexpression of HIF-1α and MT4-MMP in human head and neck cancer was predictive of a worse clinical outcome. These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis