Induction chemotherapy with dose-modified docetaxel, cisplatin, and 5-fluorouracil in Asian patients with borderline resectable or unresectable head and neck cancer

BackgroundSignificant ethnic differences in susceptibility to the effects of chemotherapy exist. Here, we retrospectively analyzed the safety and efficacy of induction chemotherapy (ICT) with dose-modified docetaxel, cisplatin, and 5-fluorouracil (TPF) in Asian patients with borderline resectable or unresectable head and neck squamous cell carcinoma (HNSCC).MethodsBased on the incidence of adverse events that occurred during daily practice, TPF90 (90% of the original TPF dosage; docetaxel 67.5 mg/m2 on Day 1, cisplatin 67.5 mg/m2 on Day 1, and 5-fluorouracil 675 mg/m2 on Days 1–5) was used for HNSCC patients who were scheduled to receive ICT TPF.ResultsBetween March 2011 and May 2014, 52 consecutive patients with borderline resectable or unresectable HNSCC were treated with ICT TPF90 followed by concurrent chemoradiotherapy. Forty-four patients (84.6%) received at least three cycles of ICT TPF90. The most commonly observed Grade 3–4 adverse events included neutropenia (35%), anemia (25%), stomatitis (35%), diarrhea (16%), and infections (13.5%). In an intention-to-treat analysis, the complete and partial response rates after ICT TPF90 were 13.5% and 59.6%, respectively. The complete and partial response rates following radiotherapy and salvage surgery were 42.3% and 25.0%, respectively. The estimated 3-year overall survival and progression-free survival rates were 41% [95% confidence interval (CI): 25–56%] and 23% (95% CI: 10–39%), respectively. The observed median overall survival and progression-free survival were 21.0 months (95% CI: 13.3–28.7 months) and 16.0 months (95% CI: 10.7–21.3 months), respectively.ConclusionTPF90 is a suitable option for Asian patients with borderline resectable or unresectable HNSCC who are scheduled for ICT

Evaluation of Plasma Charging Damage in Ultrathin Gate Oxides

Abstract-Monitoring of plasma charging damage in ultrathin oxides (e.g., <4 nm) is essential to understand its impact on device reliability. However, it is observed that the shift of several device parameters, including threshold voltage, transconductance, and subthreshold swing, are not sensitive to plasma charging and thus not suitable for this purpose. Consequently, some destructive methods, such as the charge-to-breakdown measurement, are necessary to evaluate plasma damage in the ultrathin oxides. Index Terms-Dielectric breakdown, plasma materialsprocessing applications, semiconductor device reliability

Radiotherapy for Oral Cavity Cancer

According to the National Cancer Registry of Taiwan, head and neck cancer was the fourth most common cancer and the cancer with the fourth highest mortality rate in 2011. Seventy-five percent of head and neck cancers in Taiwan are oral cavity cancers. Therefore, oral cavity cancer is an important health issue in Taiwan. Surgery is the main treatment modality, but various combinations of surgery, radiotherapy, and chemotherapy may also be used depending on the disease presentation and pathologic findings. For unresectable tumors, primary radiotherapy is the treatment of choice. Intensity-modulation, image guidance, and adaptive radiotherapy procedures can improve the radiation dose delivery and precision of the treatment. Brachytherapy and proton therapy can confine the radiation dose in limited area, which is an advantage in radiotherapy for some oral cavity cancers. In this review, we discuss the application of radiotherapy in oral cavity cancer and the advantages of different radiotherapy techniques

The Optimal Treatment Modality for Taiwan Oral Cavity Cancer Patients-Experience of a Medical Center

Oral cavity cancer ranks sixth in cancer incidence in Taiwan, and it is the most common malignancy diagnosed in Taiwanese men aged between 30 and 50 years. Despite recent declines in high risk habits, the incidence of oral cavity cancer in Taiwan is still increasing with more than 5000 new cases diagnosed in 2011. Currently, the main treatment modality for oral cavity cancer is surgical excision, either with or without adjuvant therapy. The National Comprehensive Cancer Network (NCCN) guideline is the most widely accepted guideline for head and neck cancer including oral cavity cancer. However, NCCN guidelines do not specify a definite treatment for T4b oral cavity cancer, which is not uncommon in Taiwan. In this study, we investigated current oral cavity cancer treatments in Taiwan, compared these treatments with those stipulated by the NCCN guideline, and made recommendations on the most optimal treatment for Taiwan patients

Pre-radiotherapy PSA Level as a Predictor for Biochemical Control in Prostate Cancer Patients Receiving Radiotherapy after Radical Prostatectomy

Background: To report the outcome of patients receiving radiotherapy (RT) after radical prostatectomy (RP). Methods: Between May 2001 and December 2008, 53 consecutive cases of prostate adenocarcinoma treated with RP and RT were reviewed. Results: A total of 49 patients were eligible for this study. After a median follow-up of 53 months, the 4-year overall survival (OS) and biochemical progression-free survival (bPFS) for all patients were 91.0% and 68.9%, respectively. According to univariate and multivariate analysis, pre-RT prostate-specific antigen (PSA) was the most significant factor for bPFS. Patients with pre-RT PSA levels of < 0.2 ng/ml and ≧ 0.2 ng/ml had a 4-year bPFS of 83.1% and 52.6%, respectively (p = 0.013). The incidence of chronic rectal toxicity was low, with no grade 3 toxicity reported and grade 2 toxicity found in only 6 patients (12.2%). However, long-term urinary toxicity of grade 2 or higher was found in 24 patients (49.0%). Conclusion: For patients with increasing PSA levels following RP, local RT should be administered prior to biochemical failure (PSA ≧ 0.2), to ensure good bPFS

Tumor Suppressor miRNA-503 Inhibits Cell Invasion in Head and Neck Cancer through the Wnt Signaling Pathway via the WNT3A/MMP Molecular Axis

Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion

MYH9 Facilitates Cell Invasion and Radioresistance in Head and Neck Cancer via Modulation of Cellular ROS Levels by Activating the MAPK-Nrf2-GCLC Pathway

The MYH9 (Myosin heavy chain 9), an architecture component of the actomyosin cytoskeleton, has been reported to be dysregulated in several types of cancers. However, how this molecule contributes to cancer development is still obscure. This study deciphered the molecular function of MYH9 in head and neck cancer (HNC). Cellular methods included clonogenic survival, wound-healing migration, and Matrigel invasion assays. Molecular techniques included RT-qPCR, western blot, luciferase reporter assays, and flow cytometry. Clinical association studies were undertaken by TCGA data mining, Spearman correlation, and Kaplan-Meier survival analysis. We found that MYH9 was overexpressed in tumors and associated with poor prognosis in HNC patients. MYH9 promoted cell motility along with the modulation of the extracellular matrix (fibronectin, ITGA6, fascin, vimentin, MMPs). Also, MYH9 contributed to radioresistance and was related to the expression of anti-apoptotic and DNA repairing molecules (XIAP, MCL1, BCL2L1, ATM, RAD50, and NBN). Mechanically, MYH9 suppressed cellular ROS levels, which were achieved by activating the pan-MAPK signaling molecules (Erk, p38, and JNK), the induction of Nrf2 transcriptional activity, and the up-regulation of antioxidant enzymes (GCLC, GCLM, GPX2). The antioxidant enzyme GCLC was further demonstrated to facilitate cell invasion and radioresistance in HNC cells. Thus, MYH9 exerts malignant functions in HNC by regulating cellular ROS levels via activating the MAPK-Nrf2-GCLC signaling pathway. As MYH9 contributes to radioresistance and metastasis, this molecule may serve as a prognostic biomarker for clinical application. Furthermore, an in vivo study is emergent to support the therapeutic potential of targeting MYH9 to better manage refractory cancers