Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study.

Background: Concurrent chemoradiotherapy (CCRT) is superior to radiotherapy alone for treating locoregionally advanced nasopharyngeal carcinoma (NPC). Whether adding induction chemotherapy (IC) further improves the outcome warrants investigation. Patients and methods: This open-label multicenter phase III trial was conducted at 11 institutions in Taiwan. Patients with stage IVA or IVB NPC were randomized to receive IC followed by CCRT (I-CCRT) or CCRT alone. Patients in the I-CCRT arm received three cycles of mitomycin C, epirubicin, cisplatin, and 5-fluorouracil/leucovorin (MEPFL). All patients received 30 mg/m2 cisplatin weekly during radiotherapy, which was delivered as 1.8-2.2 Gy per fraction with five daily fractions per week, to a total dose of 70 Gy or greater to the primary tumor and 66-70 Gy to the involved neck. The primary end point was disease-free survival (DFS). Results: In this study, 240 and 239 patients were randomized to CCRT and I-CCRT arm, respectively. The most prominent toxicities of induction were leukopenia (grade 3 and 4: 47% and 12%) and thrombocytopenia (grade 3 and 4: 24% and 3%). During radiotherapy, severe mucositis was the major side-effect in both arms; an increased number of patients in the I-CCRT arm had myelosuppression; hence, discontinuation of weekly cisplatin was more common. After a median follow-up of 72.0 months, the I-CCRT arm had significantly higher DFS than that of the CCRT arm [5-year rate 61% versus 50%; hazard ratio=0.739, 95% confidence interval (CI)=0.565-0.965; P = 0.0264], after stratified for N3b and LDH, and adjusted for T stage. Conclusion: Induction with MEPFL before CCRT was tolerable and significantly improved the DFS of patients with stage IVA and IVB NPC though overall survival not improved. Clinical trial information: NCT00201396.

The effectiveness of a saline mouth rinse regimen and education programme on radiation-induced oral mucositis and quality of life in oral cavity cancer patients: A randomised controlled trial.

Radiation therapy (RT) and concurrent chemotherapy RT (CCRT) generate radiation-induced oral mucositis (OM) and lower quality of life (QOL). This study assessed the impact of a saline mouth rinse regimen and education programme on radiation-induced OM symptoms, and QOL in oral cavity cancer (OCC) patients receiving RT or CCRT. Ninety-one OCC patients were randomly divided into a group that received saline mouth rinses and an education programme and a control group that received standard care. OM symptoms and QOL were assessed with the WHO Oral Toxicity Scale, MSS-moo and UW-QOL. Data were collected at the first postoperative visit to the radiation department (T0) and at 4 weeks and 8 weeks after beginning RT or CCRT. Patients in both groups had significantly higher levels of physical and social-emotional QOL at 8 weeks after beginning RT or CCRT compared to the first visit. Patients in the saline rinse group had significantly better physical and social-emotional QOL as compared to the standard care group at 8 weeks. Radiation-induced OM symptoms and overall QOL were not different between the groups. We thus conclude the saline rinse and education programme promote better physical and social-emotional QOL in OCC patients receiving RT/CCRT.

Factors associated with healthcare professional's rating of disfigurement and self-perceived body image in female patients with head and neck cancer.

The purpose of this study was to determine factors associated with self-perceived body image in female patients with head and neck cancer (HNC), and factors associated with healthcare professional's rating of disfigurement, as well as the correlation between patient and observer ratings. This cross-sectional study recruited 105 women with HNC at a large medical centre. Measures of facial disfigurement and body image, as well as demographic and clinical characteristics, were collected. Multivariate multiple linear regression modelling was used to identify factors associated with healthcare professional's rating of disfigurement and patient self-perceived body image. Disfigurement ratings by healthcare professionals were positively associated with patient self-perceived body image. Medical treatment, cancer stage, radiation dose and cancer site were significantly associated with disfigurement. Medical treatment was an important predictor of perceived body image. These findings indicate a moderate prevalence of disfigurement among women with HNCs. Patients with more disfigurement were more likely to have dissatisfaction with their body image. Nursing professionals need to carefully assess the appearance of women with HNC. Camouflage interventions can be used to help appropriately cope with the disfigurement, and to achieve improved satisfaction with their body image.

Association of HPV infections with second primary tumors in early-staged oral cavity cancer.

OBJECTIVE: The infection of human papilloma virus (HPV) has been reported in head and neck cancer; however, the clinical significance of HPV infection on the pathogenesis of oral cavity squamous cell carcinoma (OSCC) is still uncertain. MATERIALS AND METHODS: The study recruited 103 patients with pathological early-stage OSCC between March 1997 and December 2003 from Chang Gung Memorial Hospital, Taiwan. Tumor specimens were HPV-genotyped by the EasychipVR HPV Blot method. Clinical association study was performed by using chi-square, Kaplan-Meier, and logrank tests. RESULTS: Thirty-one patients (30.1%) were positive for HPV infection. The most frequent HPV types were types 16 (16 patients, 51.6%) and 18 (seven patients, 22.6%). HPV infection was not associated with tumor aggressiveness (pathological tumor stage or differentiation status), risk exposure (alcohol, cigarette, or areca quid chewing habit), or the treatment outcome (disease-free survival or overall survival). However, infection with HPV-18 was associated with the occurrence of a second primary cancers (P = 0.033), indicating the infection of HPV in OSCC enhances the susceptibility of developing secondary malignancy. CONCLUSIONS: There are 30% of the patients with OSCC infected with HPV, with most high-risk types. HPV-18 infection may enhance the susceptibility of second primary tumors. Large scale of validation study will be needed to confirm this result.

Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers.

Infection with high-risk types (type 16 or type 18) of human papillomaviruses (HPVs) increases a patient's risk of cervical cancer. Given the importance of the cervix and the severe side effects resulting from traditional cancer therapies, this study aimed to achieve targeted inhibition of viral oncogenes in tumor cells using small interfering RNAs (siRNA). To accomplish this, we developed nine siRNAs against either the E6 or E7 genes of HPV-16 or HPV-18 in several combinations, yielding siRNAs targeting 16E6, 16E7, 18E6 and 18E7. We measured the effectiveness of the siRNAs by examining E6 or E7 mRNA expression after transfection of the siRNAs into HPV-positive CaSki (HPV-16) or HeLa (HPV-18) cell lines. We found that the HPV-siRNAs significantly reduced cell growth and colony formation in both cell lines. Flow cytometry analysis revealed a significant increase in apoptosis. The siRNAs had no effect on cell growth, colony formation or apoptosis in HPV-negative C33A cells, demonstrating a lack of off-target effects. In addition, an in vivo xenograft study showed that intra-tumoral injection of the siRNAs reduced tumor growth in BALB/c nude mice. In conclusion, we have developed highly specific and potent HPV-siRNAs that successfully suppress tumor growth and induce apoptosis in HPV-positive cervical cancer cells. siRNA treatment has potential for further development as an adjuvant therapy for cervical cancer.

p53 polymorphisms associated with mutations in and loss of heterozygosity of the p53 gene in male oral squamous cell carcinomas in Taiwan.

The present study was designed to examine whether different p53 haplotypes of exon 4-intron 3-intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly higher frequency of p53 mutations than those with two Pro-W-G alleles (odds ratio (OR) = 1.98; 95% confidence interval (CI), 1.10-3.56). Out of the 172 p53 gene exon 4 informative male OSCCs, 72 (41.9%) showed LOH. Among these 72 OSCCs with LOH, the frequency of Pro allele loss was 73.6% (53/72). It is notable that alcohol drinking increased the frequency of Arg allele loss (OR = 10.56; 95% CI, 1.23-234.94) in OSCCs from patients who both smoked cigarettes and chewed areca quid (AQ). The frequency of LOH of p53 was not different between p53-mutated OSCCs and p53-normal OSCCs. Thus, the present study revealed that (a) the Arg allele is associated with p53 mutations, (b) the Pro allele is preferentially lost in OSCCs associated with cigarette smoking and AQ chewing, while the frequency of Arg allele loss is increased with alcohol drinking, and (c) haploinsufficiency of p53 is in itself likely to contribute to tumour progression in Taiwanese OSCCs.

Fluoroscopically guided percutaneous gastrostomy with modified gastropexy and a large-bore balloon-retained catheter in patients with head and neck tumors.

PURPOSE: To report on fluoroscopically guided percutaneous gastrostomy (FPG) using a modified gastropexy technique with the insertion of a large-bore balloon-retained gastrostomy catheter in patients with head and neck tumors. MATERIAL AND METHODS: Thirty-four patients with head and neck tumors underwent a modified gastropexy with two T-fasteners followed by the insertion of a 14-F ballooon-retained catheter through a peel-away introducer. The success rate and the complications of the procedures were evaluated at 14 days, 30 days, and 60 days. The complications were classified as: major complications that necessitated intensive and/or surgical treatment; minor complications that could be treated conservatively; and tube-related complications manageable by tube exchange. RESULTS: FPG was technically successful in all cases. There were no major complications, two minor complications where superficial stoma infection was controlled by antibiotics, three minor tube-related complications, all three easily managed by catheter replacement via the original tract. CONCLUSION: FPG with insertion of a large-bore balloon-retained catheter using a modified gastropexy technique is a safe and effective method that creates a feeding access for patients with head and neck tumors and esophageal obstruction. Minor complications can be managed conservatively. FPG may be a good alternative to surgical or percutaneous endoscopic gastrostomy.