METHODS: To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716).
RESULTS: Firstly, the proportion of variance of X-linked loci over phenotypic variance was estimated in the discovery samples, which revealed that the phenotypic variance explained by X chromosome polymorphisms was estimated to be 12.63% (non-dosage compensation model) in males, as compared with 0.0001% in females. This suggested that the contribution of X chromosome to the genetic variance of NPC should not be neglected. Secondly, association analysis revealed that rs5927056 in DMD gene achieved X chromosome-wide association significance in the discovery sample (OR = 0.81, 95% CI 0.73-0.89, P = 1.49 × 10-5). Combined analysis revealed rs5927056 for DMD gene with suggestive significance (P = 9.44 × 10-5). Moreover, the female-specific association of rs5933886 in ARHGAP6 gene (OR = 0.62, 95%CI: 0.47-0.81, P = 4.37 × 10-4) was successfully replicated in Taiwan Chinese (P = 1.64 × 10-2). rs5933886 also showed nominally significant gender × SNP interaction in both Guangdong (P = 6.25 × 10-4) and Taiwan datasets (P = 2.99 × 10-2).
CONCLUSION: Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.
METHOD: This was a retrospective clinical record review study carried out at a tertiary centre from June 2013 until May 2017. A total of 55 locally recurrent NPC patients (rT1-rT4) underwent EETN performed by single skull base surgeon with curative intention with postoperative adjuvant chemotherapy but without postoperative radiotherapy.
RESULTS: There were 44 (80.0%) males and 11 (20.0%) females, with mean age of 52.5 years. The mean operating time was 180 min (range 150-280 min). 85% (47/55) of patients achieved en bloc tumour resection. 93% (51/55) of patients obtained negative microscopic margin based on postoperative histopathological evaluation. Intraoperatively, one (1.8%) patient had internal carotid artery injury which was successfully stented and had recovered fully without neurological deficit. There were no major postoperative complications reported. During a mean follow-up period of 18-month (range 12-48 months) postsurgery, five patients (9.1%) had residual or recurrence at the primary site. All five patients underwent re-surgery. One patient at rT3 passed away 6 months after re-surgery due to distant metastasis complicated with septicaemia. The 1-year local disease-free rate was 93% and the 1-year overall survival rate was 98%.
CONCLUSIONS: EETN is emerging treatment options for locally recurrent NPC, with relatively low morbidity and encouraging short-term outcome. Long-term outcome is yet to be determined with longer follow-up and bigger cohort study. However, a successful surgical outcome required a very experienced team and highly specialised equipment.
METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.
RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.
CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.
METHODS: A total of 159 patients with non-metastatic nasopharyngeal carcinoma treated during 2002-2003 in Hospital Kuala Lumpur were included in this study. All received radiotherapy. Fifty three patients were treated with radiotherapy alone, while 106 patients received combination chemotherapy. Overall survival and local recurrence-free survival were analyzed using the Kaplan-Meier method and univariate analysis was performed using the log-rank test.
RESULTS: This study found out that 5-year overall survival and 5-year local recurrence-free survival rates were 58.6% and 54.2% respectively. The stage specific 5-year overall survival rates were: Stage I, 100%; Stage II; 93.3%, Stage III, 62.7%; Stage IVA, 42.2%; and Stage IVB, 40.6%. On univariate analysis, gender (p<0.05), T-classification (p<0.001), N-classification (p<0.05), stage (p<0.05) and cranial nerve involvement (p<0.001) were found to be significant prognostic factors for 5-year overall survival, while gender (p<0.05) and N-classification (p<0.05) were significant prognostic factors for 5-year local recurrence-free survival.
CONCLUSION: The overall survival rate of patients for this study was low. The patient factor that significantly affected 5-year overall survival was gender, while disease factors were stage, T-classification, N-classification and cranial nerve involvement.
MATERIALS AND METHODS: The cancer registry from 1986 to 2014 maintained by the State Laboratory was retrospectively reviewed. The age standardized rates (ASR) and the age specific incidence rates (ASIR) were calculated. Non NPC tumors were excluded from the study.
RESULTS: Altogether, there were a total of 450 NPC cases diagnosed accounting for 4.4% of all total cancer cases over the study period, declining from 10.3% in 1986-1990 to 2.3% in 2011-2014. The most common tumor type was the undifferentiated carcinoma (96.4%). The case characteristics were mean age 50.4 ± 14.4 years old, male 69%, and predominately Malays 74.4%, followed by Chinese 16.7%. The mean age of diagnosis increased over the study period from 45.6 ± 17.1 years (1986-1989) to 54.1 ± 12.5 years (ANOVA, p<0.01 for trend). There were no differences in the mean age of diagnosis between the ethnic groups or genders. The ASR showed a declining trend from 11.1 per 100,000 in 1986-1990 to 5.95 per 100,000 in 2011-2014, similar trends been observedfor both genders. Among the age groups, declining trends were seen in all the other age groups apart from the >70 years group. The overall ASRs for the Malays and Chinese were 7.92/100,000 and 8.83/100,000 respectively, both showing declining trends.
CONCLUSIONS: The incidence of NPC in Brunei Darussalam is comparable to rates reported from Singapore and Malaysia, but higher than rates reported from the other Southeast Asian nations. Unlike higher rates reported for Chinese compared to the Malays in other countries, the rates between the Malays and Chinese in our study was comparable. Importantly, the ASR is declining overall and for both genders and ethnic groups.