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Purpose: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC. Methods: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified. Updated data were sought for studies included in the previous rounds of the meta-analysis. The primary endpoint was overall survival. All trials were analyzed following the intent-to-treat principle using a fixed-effects model. Treatments were classified in five subsets according to chemotherapy timing. The statistical analysis plan was pre-specified. Results: Eighteen new trials were identified. Individual patient data were available for seven. In total, the meta-analysis now included 26 trials and 7,080 patients. The addition of chemotherapy reduced the risk of death, with a hazard ratio (HR) of 0.79 (95% confidence interval (CI) [0.73; 0.85]), and an absolute survival increase at 5 and 10 years of 6.1% [+3.9; +8.3] and + 8.4% [+5.7; +11.1], respectively. The largest effect was observed for concomitant + adjuvant, induction (with concomitant in both arms) and concomitant chemotherapy, with respective HR [95%CI] of 0.68 [0.59; 0.79] (absolute survival increase at 5 years: 12.3% (7.0%;17.6%)), 0.73 [0.63; 0.86] (6.0% (2.5%;9.5%)) and 0.81 [0.70; 0.92] (5.2% (0.8%;9.6%)). The benefit of chemotherapy was also demonstrated by improvement in progression-free survival, cancer mortality, locoregional control and distant control. There was a significant interaction between patient age and chemotherapy effect. Conclusion: This updated meta-analysis confirms the benefit of concomitant chemotherapy and concomitant + adjuvant chemotherapy, and suggests that addition of induction or adjuvant chemotherapy to concomitant chemotherapy improves tumor control and survival. The benefit of chemotherapy decreases with increasing patient age.

Abstract Germline polymorphisms are linked with differential survival outcomes in cancers but are not well studied in nasopharyngeal carcinoma (NPC). Here, a two‐phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome‐wide genotypes at 246 173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazard regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta‐analysis of all samples (n = 5553) confirms that the presence of rs1131636‐T, located in the 3′‐UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20–1.47, P = 6.31 × 10−8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promotes the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR‐1253 is identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.

We here report the first case in the literature on a surgical emergency of complete small bowel obstruction caused by metastasis from nasopharyngeal carcinoma nine months after the primary tumor was treated with concurrent chemoradiation. The patient achieved prolonged survival with prompt surgical treatment followed by systemic chemotherapy.

Micrometastases in lymph nodes and blood may provide important prognostic information. In this study, cytokeratin 20 (CK20) positive cells in lymph nodes and circulating CK20 mRNA were studied using 57 paraffin-embedded lymph node specimens and blood from 24 patients with pN0 colorectal cancer (CRC), respectively. Results showed that 29 out of 56 (52%) lymph node specimens had CK20-positive cells (range: 1-35). Follow-up of the patients for 12 months indicated that 4 patients (7%) had CRC metastases to liver, lung, and bone. In addition, 8 out of 24 (33%) samples had at least 2-fold circulating CK20 mRNA expression higher than the pooled normal sample. This study provides evidence that CK20-positive cells were found in the lymph nodes and differentially expressed circulating CK20 mRNA was also detected in the blood from patients with pN0 CRC. Long-term follow-up is necessary to study their prognostic use in patients with nonmetastatic CRC. [ABSTRACT FROM AUTHOR]

Background: Single-agent doxorubicin has been widely used to treat unresectable hepatocellular carcinoma (HCC), but the response rate is low («20%) and there is no convincing evidence for improved survival. Cisplatin, interferon, doxorubicin, and fluorouracil (PIAF) used in combination, by contrast, has shown promise in a phase II study. We compared doxorubicin to PIAF in patients with unresectable HCC in a phase III trial. Methods: Patients with histologically confirmed unresectable HCC were randomly assigned to receive either doxorubicin or PIAF every 3 weeks, for up to six cycles. The primary endpoint was overall survival, and secondary endpoints were response rate and toxicity. Survival differences were calculated using the Kaplan-Meier method. Treatment groups were compared for differences in the incidence of adverse events using chi-square tests. All statistical tests were two-sided. Results: The median survival of the doxorubicin and PIAF groups was 6.83 months (95% confidence [CI] = 4.80 to 9.56) and 8.67 months (95% CI = 6.36 to 12.00), respectively (P = 0.83). The hazard ratio for death from any cause in the PIAF compared with the doxorubicin groups was 0.97 (95% CI = 0.71 to 1.32). Eighty-six of the 94 patients receiving doxorubicin and 91 of the 94 receiving PIAF were assessable for response. The overall response rates in the doxorubicin and PIAF groups were 10.5% (95% CI = 3.9% to 16.9%) and 20.9% (95% CI = 12.5% to 29.2%), respectively. Neutropenia, thrombocytopenia, and hypokalemia were statistically significantly more common in patients treated with PIAF than in patients treated with doxorubicin. Conclusion: Although patients on PIAF had a higher overall response rate and better survival than patients on doxorubicin, the differences were not statistically significant. PIAF was also associated with increased treatment-related toxicity. The prognosis of patients with unresectable HCC remains poor. [ABSTRACT FROM AUTHOR]

Micrometastases in lymph nodes and blood may provide important prognostic information. In this study, cytokeratin 20 (CK20) positive cells in lymph nodes and circulating CK20 mRNA were studied using 57 paraffin-embedded lymph node specimens and blood from 24 patients with pN0 colorectal cancer (CRC), respectively. Results showed that 29 out of 56 (52%) lymph node specimens had CK20-positive cells (range: 1-35). Follow-up of the patients for 12 months indicated that 4 patients (7%) had CRC metastases to liver, lung, and bone. In addition, 8 out of 24 (33%) samples had at least 2-fold circulating CK20 mRNA expression higher than the pooled normal sample. This study provides evidence that CK20-positive cells were found in the lymph nodes and differentially expressed circulating CK20 mRNA was also detected in the blood from patients with pN0 CRC. Long-term follow-up is necessary to study their prognostic use in patients with non-metastatic CRC.