Population-based nasopharyngeal carcinoma survival in southern China.

Prediagnostic use of menopausal hormone therapy (MHT) has been suggested to be associated with improved survival of epithelial ovarian cancer (EOC). We investigated the potential long‐term survival benefit of prediagnostic MHT use in women ≥50 years with nonlocalized EOC using the Extreme study including all women in Denmark registered with nonlocalized EOC during 2000 to 2014 (N = 3776). We obtained individual‐level information on prediagnostic use of systemic estrogen therapy (ET) and estrogen plus progestin therapy (EPT) from the National Prescription Registry and estimated absolute and relative 5‐ and 10‐year survival probabilities with 95% confidence intervals (CIs) using pseudo‐values, taking into account histology, comorbidity, income and residual disease. Among women not having used prediagnostic MHT, 5‐ and 10‐year absolute survival probabilities were 19% and 11%, respectively. Compared to MHT nonusers, prediagnostic systemic ET use for 3 to 4 years and ≥ 5 years was associated with 1.43 (95% CI: 1.01‐2.02) and 1.22 (95% CI: 0.96‐1.55) times higher 5‐year survival probabilities, respectively. Ten‐year survival probabilities were also increased but not statistically significantly. Among prediagnostic EPT users, increased 5‐year (1.14, 95% CI: 0.85‐1.53) and 10‐year (1.38, 95% CI: 0.91‐2.08) survival probabilities were observed after use for 3 to 4 years compared to MHT nonuse, whereas EPT use for ≥5 years was not associated with long‐term survival of nonlocalized EOC. Our findings may suggest a better long‐term survival of nonlocalized EOC in women having used long‐term prediagnostic ET. However, the statistical precision of our results did not allow firm conclusions and more studies are needed.

1458PD - Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer: 10-year follow-up of West Japan thoracic oncology group WJTOG0105

An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated. This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake. Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79). Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.

Natural History of Patients Hospitalized for Management of Cirrhotic Ascites

NOLC1, an Enhancer of Nasopharyngeal Carcinoma Progression, Is Essential for TP53 to Regulate MDM2 Expression

Nasopharyngeal carcinoma (NPC) is different from other head and neck squamous cell carcinomas and is closely related with Epstein-Barr virus infection. It is endemic in southern China and Southeast Asia, affecting between 20 and 30 per 100,000 populations. According to the World Health Organization (WHO) histological classification, there are three subtypes of NPC: WHO type 1 NPC is keratinizing squamous cell carcinoma; type 2 NPC is differentiated non-keratinizing carcinoma; type 3 NPC is undifferentiated non-keratinizing carcinoma. In southern China including Hong Kong, type 3 NPC (undifferentiated NPC) is dominant and constitutes over 90% of the total NPC. MicroRNA-138 (miR-138) is a small non-coding RNA which has been reported to be highly expressed in undifferentiated NPC. We hereby evaluated whether the miR-138 level could be used to differentiate NPC patients from the normal individuals and examine the potential oncogenic role in undifferentiated NPC cell line. To validate the hypothesis that miR-138 was an oncogenic microRNA, which is overexpressed in undifferentiated NPC patients, we first examined its expression level in nasopharyngeal tissues and peripheral blood. In our cohort, cancer tissues samples were collected from 42 primary NPC and 29 recurrent NPC patients. To evaluate the expression level in the cancer tissues, the miR-138 level was quantified by real-time quantitative polymerase chain reaction. For primary NPC, the expression level was compared with 29 normal nasopharyngeal epithelia. For recurrent NPC, the microRNA level was compared with the paired normal mucosa counterparts obtained from the same patients. In addition, plasma samples were also collected from 22 primary NPC, 21 recurrent NPC and 17 normal individuals. Our data suggested that there was no difference in the miR-138 expression level in primary NPC tissue and normal nasopharyngeal tissue from control. There was no difference in the circulating miR-138 levels in the primary NPC, recurrent NPC and normal control groups. The circulating miR-138 could not be used to differentiate NPC patients from the normal individuals. Further functional analysis on the undifferentiated NPC cell line HONE1 suggested that miR-138 overexpression could enhance NPC cell proliferation, migration and invasion in comparison with the mock control. With the use of high-throughput gene expression arrays, we observed that multiple cancer-related pathways were affected in miR-138 overexpressed NPC cells. Staining with Acridine orange (AO) and phosphorylated H2AX (γH2AX) showed that miR-138 overexpression is associated with an enhanced response to radiation. Our results are concordant with other similar studies suggested that miR-138 is an oncogenic microRNA which play an important part in the undifferentiated NPC tumorigenesis. Further studies, based on larger sample size, are warranted to explore the clinical use of this small RNA in diagnosis, prognosis and management of undifferentiated NPC.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of approximately 90%. However, NPC is typically diagnosed at advanced stages, in which disease-free survival is <50%. There is, therefore, a need for clinical tools to assist in early NPC detection, particularly among high-risk individuals. We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (N = 21) and age- and sex-matched controls (N = 84) were selected. Serum collected before NPC diagnosis was tested for ELISA-based IgA antibodies against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated. EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected. EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives. Results from this study could inform decisions about screening biomarkers and referral thresholds for future NPC early-detection program evaluations.

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)–associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of approximately 90%. However, NPC is typically diagnosed at advanced stages, in which disease-free survival is &lt;50%. There is, therefore, a need for clinical tools to assist in early NPC detection, particularly among high-risk individuals.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (&lt;i&gt;N&lt;/i&gt; = 21) and age- and sex-matched controls (&lt;i&gt;N&lt;/i&gt; = 84) were selected. Serum collected before NPC diagnosis was tested for ELISA-based IgA antibodies against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Impact:&lt;/b&gt; Results from this study could inform decisions about screening biomarkers and referral thresholds for future NPC early-detection program evaluations. &lt;i&gt;Cancer Epidemiol Biomarkers Prev; 23(7); 1213–9. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)–associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of approximately 90%. However, NPC is typically diagnosed at advanced stages, in which disease-free survival is &lt;50%. There is, therefore, a need for clinical tools to assist in early NPC detection, particularly among high-risk individuals.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (&lt;i&gt;N&lt;/i&gt; = 21) and age- and sex-matched controls (&lt;i&gt;N&lt;/i&gt; = 84) were selected. Serum collected before NPC diagnosis was tested for ELISA-based IgA antibodies against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Impact:&lt;/b&gt; Results from this study could inform decisions about screening biomarkers and referral thresholds for future NPC early-detection program evaluations. &lt;i&gt;Cancer Epidemiol Biomarkers Prev; 23(7); 1213–9. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

Almost 500,000 women are newly diagnosed with cervical cancer (CC) every year, the majority from developing countries. There is little information on the survival of these patients. Our primary objective was to evaluate consecutive CC patients presenting over 4 years at the only radiotherapy center in Ethiopia. All patients with CC from September 2008 to September 2012 who received radiotherapy and/or surgery were included (without brachytherapy). Vital status was obtained through telephone contact or patient cards. Of 2,300 CC patients, 1,059 patients with standardized treatment were included. At the end of the study, 249 patients had died; surviving patients had a median follow-up of 16.5 months; the 10% and 90% percentiles were 3.0 and 32.7 months, respectively. Mean age was 49 years (21-91 years). The majority of patients presented with International Federation of Gynecology and Obstetrics stage IIb-IIIa (46.7%). Because of progression during the waiting time (median 3.8 months), this proportion declined to 19.3% at the beginning of radiotherapy. The 1- and 2-year overall survival probabilities were 90.4% and 73.6%. If assuming a worst-case scenario (i.e., if all patients not available for follow-up after 6 months had died), the 2-year survival probability would be 45.4%. This study gives a thorough 4-year overview of treated patients with CC in Ethiopia. Given the limited treatment availability, a relatively high proportion of patients survived 2 years. More prevention and early detection at all levels of the health care system are needed. Increasing the capacity for external-beam radiation as well as options for brachytherapy would facilitate treatment with curative intention.

BACKGROUND: Childhood brain tumors are the most common solid neoplasm and the leading cause of cancer-related morbidity and mortality in children. OBJECTIVES: To determine which patient and tumor characteristics are predictive of good outcome in patients with posterior fossa tumors. DESIGN: Analytical retrospective, cross sectional study. SETTING: Tertiary level hospital. PATIENTS: Total of 85 charts of children with posterior fossa tumors admitted at PCMC from 2004 to 2013 were reviewed. MAIN OUTCOME MEASURE(S): Patient and tumor characteristics were determined and analyzed using univariate analysis. Age, extent of tumor resection, and tumor histology were analyzed if predictive of poor outcome. One-year and 3-year overall survival probability were analyzed using the Kaplan-Meier estimation method. Mantel-Cox Log-Rank Overall Comparisons was used to identify prognostic variables for over-all survival. RESULTS: Medulloblastoma is the most common tumor at 62%, pilocytic astrocytoma 23% and ependymoma 11%. Majority belongs to the 36months and older age group with male predominance at 1.36:1. Most common signs and symptoms were headache, vomiting and ataxia. The 1-year and 3-year overall survival probability are 61% and 41%, respectively. Univariate analysis showed that clinical outcome was significantly correlated with gender (female associated with good clinical outcome, p = 0.022) and histologic tumor types (medulloblastoma associated with poor outcome; pilocytic astrocytoma with good outcome, p = 0.012). Gender and histologic tumor types and brainstem involvement were identified as significant factors for 1- and 3-year overall survival (p = 0.049, p = 0.008, and p = 0.029). CONCLUSION: Gender and histologic type of tumors are significant prognostic factors for both the clinical outcome and overall 1-year and 3-year survival probability. Brainstem involvement is a significant prognostic variable for overall survival. One- and three-year overall survival rates are 61 % and 41%, respectively. The need to formulate an institutional tumor guideline to ensure standard treatment and follow-up of these patients are necessary.

Elderly patients who present with acute myocardial infarction are at increased risk for adverse outcomes owing to higher comorbidity burden and complicated coronary anatomy. We evaluated the three-year outcomes following coronary revascularization compared to conservative management among elderly patients presenting with acute myocardial infarction. 155 patients over 75 years of age who were admitted for acute myocardial infarction underwent invasive treatment with coronary angioplasty (n=58) or only medical treatment (n=97). The Kaplan-Meier log rank test was used to compare 3-year survival and rehospitalization probability and the Mantel-Cox log rank test was used to compare mean survival time between groups. In the Invasive treatment group (ITG) cohort, 3-year survival probability was 74.1% as compared to 29.9% in the Conservative treatment group (CTG) cohort (P<0.001). Mean survival time at 3 years of follow-up was 31.50 (95% CI 29.35-33.65) months among ITG patients versus 24.65 (95% CI 22.71-26.59) months among CTG patients (P<0.001). Mean time to rehospitalization at 3 years was 34.05 (95% CI 32.37-35.72) in the ITG cohort compared to 30.03 (95% CI 28.13-31.93) in the CTG cohort (P=0.004). Coronary revascularization among elderly patients with acute myocardial infarction reduces both all-cause mortality and cardiovascular events at 3-year follow-up. However, rates of rehospitalizations remain statistically similar between groups. Moreover, invasive treatment imparted improved rehospitalization probability compared to conservative treatment. This observation can be partially explained by a reduction in the frequency of myocardial infarction among those who underwent invasive treatment. While a thorough clinical assessment is required prior to treatment determination among elderly patients with acute myocardial infarction, coronary revascularization should be strongly considered as an intervention that likely improves overall survival probability.

We thank Lin KY et al for their comments on our manuscript entitled “Use of antibiotics during immune checkpoint inhibitors associates with lower survival in hepatocellular carcinoma”.1 Several issues were raised in the letter including the start time for survival analysis, the details of survival time with Kaplan-Meier curve and definition of cancer-related death. In the “Outcome definition” paragraph of our manuscript, it was mentioned that patients were observed from the start date of first immune checkpoint inhibitor as the index date till the occurrence of the outcome of interest or end of study. In the same paragraph, we have defined the primary outcome of cancer-related mortality as “liver cancer specified as the cause of death in the database” by the diagnosis codes. In the whole cohort, the 3-month, 6-month, 1-year and 2-year probability of cancer-related survival was 70.7% (95% CI: 66.3 – 75.4%), 57.4% (95% CI: 52.6 – 62.6%), 45.9% (95% CI: 41.1 – 51.4%) and 37.4% (32.4 – 43.3%), respectively. Figure 1 shows the Kaplan Meier survival plot of the whole cohort. Among the antibiotic users, the 3-month, 6-month, 1-year and 2-year probability of cancer-related survival was 50.9% (95% CI: 42.0 – 61.7%), 35.3% (95% CI: 26.9 – 46.4%), 26.8% (95% CI: 19.1 – 37.7%) and 19.3% (12.0 – 31.1%), respectively. For antibiotic non-users, the 3-month, 6-month, 1-year and 2-year probability of cancer-related survival was 77.8% (95% CI: 73.1 – 82.8%), 64.7% (95% CI: 59.4 – 70.6%), 52.2% (95% CI: 46.5 – 58.5%) and 43.6% (37.7– 50.5%), respectively. There was significant difference in cancer-related survival between the two groups (log-rank p &lt; 0.001). Figure 2 shows the Kaplan Meier survival plot according to antibiotic use.

Nasopharyngeal carcinoma (NPC) is a rare cancer in the United States. An association between NPC and Epstein-Barr virus (EBV) is well-established for World Health Organization (WHO) types II and III (WHO-II/III) NPC but less well-established for WHO type I (WHO-I) NPC. Given the rise in oropharyngeal tumors positive for high-risk human papillomavirus (HPV) and the unique biology of WHO-I NPC, we examined the relationship between HPV and WHO-I NPC. Retrospective case-comparison study. A search of a large multidisciplinary cancer center tumor registry identified 183 patients seen from January 1999 to December 2008 with incident NPC and no prior cancer. Available paraffin-embedded tumor specimens (N = 30) were analyzed for oncogenic HPV status by in situ hybridization (ISH) and polymerase chain reaction (PCR) for HPV-16 and HPV-18; EBV status by ISH; and p16 expression by immunohistochemistry. Demographic parameters, including race and smoking, were obtained from the medical records. Among the 18 WHO-I NPC patients, 66% (N = 12) were smokers and 17% (N = 3) Asian; among the 165 WHO-II/III NPC patients, 44% (N = 73) were smokers and 24% (N = 39) Asian. Eight WHO-I NPC patients had available paraffin blocks; five of six were HPV-16-positive by PCR and four of eight were HPV-positive by ISH; only two of eight (25%) were EBV-positive. Twenty-two WHO-II/III NPC patients had available paraffin blocks; only 1 was HPV-positive by ISH, and 13 of 22 (60%) were EBV-positive. These results suggest that WHO-I NPC is associated with oncogenic HPV, although larger studies are needed to verify these findings. Laryngoscope, 2010.

Recently, the survival rate of nasopharyngeal carcinoma (NPC) patients has improved greatly due to developments in NPC treatments. But cause-specific mortality in NPC patients remains unclear. This study aims to investigate the common causes of death in NPC patients. Eligible patients with NPC were included from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios(SMRs) were calculated to compare death rates in NPC patients with those in the general population. A total of 3475 patients with NPC were included, of whom 1696 patients died during the follow-up period. 52.83% of deaths were caused by NPC, followed by other cancers (28.13%) and non-cancer causes (18.46%). The proportion of patients who died of NPC decreased over survival time. Moreover, non-cancer causes of death increase from 12.94% to 51.22% over time after 10 years of diagnosis. Heart diseases was the most common non-cancer cause of death in NPC patients. Although NPC remains the leading cause of death after NPC diagnosis, other non-NPC causes of death represent an increased number of death in NPC patients. These findings support the involvement of multidisciplinary care for follow-up strategy in NPC patients.