A glycosylation-related signature predicts survival in pancreatic cancer.

BACKGROUND: Tumor initiation and progression are closely associated with glycosylation. However, glycosylated molecules have not been the subject of extensive studies as prognostic markers for pancreatic cancer. The objectives of this study were to identify glycosylation-related genes in pancreatic cancer and use them to construct reliable prognostic models. MATERIALS AND METHODS: The Cancer Genome Atlas and Gene Expression Omnibus databases were used to assess the differential expression of glycosylation-related genes; four clusters were identified based on consistent clustering analysis. Kaplan-Meier analyses identified three glycosylation-related genes associated with overall survival. LASSO analysis was then performed on The Cancer Genome Atlas and International Cancer Genome Consortium databases to identify glycosylation-related signatures. We identified 12 GRGs differently expressed in pancreatic cancer and selected three genes (SEL1L, TUBA1C, and SDC1) to build a prognostic model. Thereafter, patients were divided into high and low-risk groups. Eventually, we performed Quantitative real-time PCR (qRT-PCR) to validate the signature. RESULTS: Clinical outcomes were significantly poorer in the high-risk group than in the low-risk group. There were also significant correlations between the high-risk group and several risk factors, including no-smoking history, drinking history, radiotherapy history, and lower tumor grade. Furthermore, the high-risk group had a higher proportion of immune cells. Eventually, three glycosylation-related genes were validated in human PC cell lines. CONCLUSION: This study identified the glycosylation-related signature for pancreatic cancer. It is an effective predictor of survival and can guide treatment decisions.

Matched-pair analysis of the impact of low-dose postoperative radiotherapy on prognosis in patients with advanced hypopharyngeal squamous cell carcinoma without positive surgical margins and extracapsular extension.

Background: We conducted a comparative analysis between low and high-dose postoperative radiotherapy in patients with hypopharyngeal squamous cell carcinoma (HPSCC) in stage III or IV without positive surgical margins and extracapsular extension (ECE). Propensity score matching (PSM) was used to eliminate confounding factors and reduce bias. Methods: The matched-pair analysis included 156 patients divided into two groups: the low-dose radiotherapy group (LD-RT 50 Gy, 78 cases) and the high-dose radiotherapy group (HD-RT 60 Gy, 78 cases). Both cohorts were statistically comparable in terms of age, gender, subsite, and TNM classification. Results: The median follow-up time was 49 months (ranging from 5 to 100 months). The overall survival (OS) rate, progression-free survival (PFS) rate, locoregional control rate (87% vs. 85.7%; p = 0.754), distant metastases-free survival (79.2% vs. 76.6%; p = 0.506), and the occurrence of second primary tumors (96.1% vs. 93.5%; p = 0.347) showed no significant differences between the LD-RT group and the HD-RT group. The 3-year OS was 64.9% and 61% in the low-dose and high-dose group, respectively, and 63% in the entire group (p = 0.547). The 3-year PFS was 63.6% and 54.5% (p = 0.250), respectively, and the 3-year PFS of the entire group was 59.1%. Multivariate analyses revealed that pathological T and N classification, and pathological differentiation were associated with 3-year OS, PFS, and LRFS and were independent prognostic factors (p < 0.05). LD-RT was not associated with an increased risk of death and disease progression compared to HD-RT. Conclusion: The results of postoperative low-dose radiotherapy did not show inferiority to those of high-dose radiation for patients with advanced hypopharyngeal cancer without positive surgical margins and ECE in terms of OS, PFS, locoregional control, and metastases-free survival.

The efficacy and safety of PD-1 inhibitors for EGFR-mutant non-small cell lung cancer after tyrosine kinase inhibitor failure: a retrospective real-world cohort study.

Background: Acquired drug resistance to various tyrosine kinase inhibitor (TKI) inevitably develops in almost all epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). The present study aimed to evaluate the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors for such patients after TKI failure and further explore the subpopulation that exhibited the most benefit. Methods: A total of 102 EGFR-mutant NSCLC patients who received PD-1 inhibitors after developing resistance to EGFR-TKIs were included in the study. The primary endpoints were progression-free survival (PFS) and grade 3-5 adverse events (AEs), while the secondary endpoints were overall survival (OS), disease control rate (DCR) and subgroup analyses. Results: All the 102 patients received 2 or more lines of immunotherapy. The overall median PFS was 4.95 months [95% confidence interval (CI): 3.91-5.89 months]. The EGFRL858R group showed a significant PFS benefit compared with the EGFRD19 group (6.4 vs. 3.5 months, P=0.002), and likewise for the DCR between the 2 groups (EGFRL858R vs. EGFRD19 group: 84.3% vs. 66.7%, P=0.049). In addition, median PFS in the EGFRT790M-negative group (6.47 months) was significantly longer than the EGFRT790M-positive group (3.20 months) (P=0.003). The overall OS was 10.70 months (95% CI: 8.92-12.48 months), without a prognostic factor. There was a trend towards improved PFS and OS with combination therapy. The incidence of grade 3-5 treatment-related AEs was 19.6%, while the incidence of grade 3-5 immune-related AEs (irAEs) was 6.9%. Treatment-related AEs were similar in different mutation subtypes. The incidence of grade 3-5 irAEs was higher in the EGFRD19 group (10.3%) compared with the EGFRL858R group (5.9%), and likewise in the EGFRT790M-negative group (10%) compared with the EGFRT790M-positive group (2.6%). Conclusions: After EGFR-TKI failure, PD-1 inhibitors provided better survival in advanced NSCLC for the EGFRL858R subgroup and EGFRT790M-negative subgroup, and there was a trend towards improved outcomes with combination therapy. In addition, toxicity was well tolerated. Our real-world study increased the population size and obtained a similar survival outcome compared from clinical trials.

The Efficacy of Low Postoperative Radiation Dose in Patients with Advanced Hypopharyngeal Cancer without High-Risk Factors.

OBJECTIVE: To evaluate the feasibility and efficacy of low postoperative radiotherapy (PORT) dose in patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC) and identify prognostic factors in this group. PATIENTS AND METHODS: Between January 2013 and September 2015, 110 consecutive patients with HPSCC with no high-risk factors were treated postoperatively to 50 Gy (n=89), 56 Gy (n=12), and 60 Gy (n=9) in 2 Gy/fraction. Overall survival (OS), 3-year progression-free survival (PFS), 3-year loco-regional recurrence-free survival (LRFS), and treatment-related toxicities were analyzed. RESULTS: Median follow-up time was 40 months (range=6-75 months). The 3-year local-regional control (LRC) and 3-year neck control rate were 86.3% and 91.8%, respectively. The 3-year OS, PFS, and LRFS were 69.9%, 65.5%, and 80.5%, respectively. In a univariate analysis, T stage showed a significant correlation with improved OS, PFS, and LRFS (P=0.008, P=0.039, P=0.034). On multivariate analysis, T stage showed a significant correlation with improved OS and PFS. N stage showed a significant correlation with improved PFS. However, interval surgery-radiotherapy, reconstructive methods, and RT dose cannot serve as a significant prognostic factor for survival outcome. CONCLUSION: This study suggests that treating no high-risk factors for locally advanced HPSCC with a dose of 50 Gy to the whole operative bed and elective lymph node levels cannot compromise disease control and survival.

A systematic comparison of treatment modalities for nasal extranodal natural killer/T-cell lymphoma in early stages between concurrent chemoradiotherapy and sequential chemotherapy.

AIM: Nasal extranodal natural killer/T-cell lymphoma (nasal ENKTL), which is strongly associated with the Epstein-Barr virus infection, is a common disease in Asia and Latin America. We conducted a retrospective study to compare the overall survival (OS) following concurrent or sequential treatment with radiotherapy and chemotherapy in patients with early stage ENKTL. PATIENTS AND METHODS: The records of 58 cases from between 2000 to 2010 were retrieved. Of these, 28 patients (15 males, with median age of 51 years) were treated with sequential chemotherapy followed by radiotherapy (SCRT) and 30 patients (17 males, with median age of 46 years) were treated with concurrent chemoradiotherapy (CCRT). Subsequently, the OS, 5-year progression-free survival (PFS), 5-year locoregional-free survival (LRFS), and relevant toxicities were analyzed. RESULTS: There were no significant differences in the toxicities and complete response rate between the 2 groups (all P>0.05) during and immediately after treatment. Kaplan-Meier curve analysis demonstrated that there were significant differences between the CCRT and SCRT groups with regard to 5-year OS (72.9% vs 47.1%, P=0.029), 5-year PFS (68.8% vs 34.2%, P=0.030), and LRFS (78.9% vs 45.7%, P=0.026). CONCLUSION: We have demonstrated that in comparison with SCRT, CCRT significantly improves the survival outcome in patients with localized ENKTL, with acceptable toxicities. Further clinical trials are needed.

Clinical study of the time of repeated computed tomography and replanning for patients with nasopharyngeal carcinoma.

PURPOSE: To study the necessity of repeat computed tomography (CT) scan and replanning and know a more accurate time using weekly kilovoltage cone beam computed tomography (kV-CBCT) scans for patients with nasopharyngeal carcinoma (NPC) during radiotherapy. METHODS AND MATERIALS: Thirteen NPC patients treated with IMRT were enrolled into this prospective study. Weekly pretreatment kV-CBCT scans were performed on the 1st, 6th, 11st, 16th, 21st and 26th radiation time, respectively. Target delineations were contoured on all fractionated CBCT images, including the gross tumor volume of the primary nasopharyngeal tumor (GTVnx) and parotid glands. The volumes of GTVnx and parotid glands were calculated automatically using the Pinnacle3 8.0 system. Compared to the original GTVnx, the percentage of shrinking volume (ΔP) ≥ 50% was considered significantly. RESULTS: As the radiation proceeding, the GTVnx had a trend of shrinkage. Of all 13 patients, 11 cases (84.6%) had the volume shrinking ≥ 50% before the 21st radiation and 12 cases (92.3%) before the 26th radiation. And the parotid volume decreased significantly in the first four-week radiation, 6.45 ± 3.16cm3 (range, 3.06-13.9cm3) for the left parotid gland and 5.78 ± 2.39cm3 (range, 2.70-11.2cm3) for the right. Furthermore, only a little displacement occurred to bilateral parotid glands. CONCLUSION: The replanning for NPC patients with IMRT is necessary, and the time between the 21st to 25th radiations is appropriate.

Comparison of long-term survival between temozolomide-based chemoradiotherapy and radiotherapy alone for patients with low-grade gliomas after surgical resection.

PURPOSE: This study was designed to compare the survival outcomes of temozolomide-based chemoradiotherapy (TMZ + RT) vs radiotherapy alone (RT-alone) for low-grade gliomas (LGGs) after surgical resection. PATIENTS AND METHODS: In this retrospective analysis, we reviewed postoperative records of 69 patients with LGGs treated with TMZ + RT (n=31) and RT-alone (n=38) at the Shandong Cancer Hospital Affiliated to Shandong University between June 2011 and December 2013. Patients in the TMZ + RT group were administered 50-100 mg oral TMZ every day until the radiotherapy regimen was completed. RESULTS: The median follow-up since surgery was 33 months and showed no significant intergroup differences (P=0.06). There were statistically significant intergroup differences in the progression-free survival rate (P=0.037), with 83.9% for TMZ-RT group and 60.5% for RT-alone group. The overall 2-year overall survival (OS) rate was 89.86%. Age distribution (≥45 years and <45 years) and resection margin (complete resection or not) were significantly associated with OS (P=0.03 and P=0.004, respectively). CONCLUSION: Although no differences were found in the 2-year OS between the TMZ + RT and RT-alone groups, there was a trend toward increased 2-year progression-free survival in the TMZ + RT group. With better tolerability, concurrent TMZ chemoradiotherapy may be beneficial for postoperative patients with LGGs. Age distribution and surgical margin are likely potential indicators of disease prognosis. The possible differences in long-term survival between the two groups and the links between prognostic factors and long-term survival may be worthy of further investigation.

Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma.

AIM: In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF) have been involved in the treatment of nasopharyngeal carcinoma (NPC). However, the potential clinical effects and toxicities are still controversial. METHODS: Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS), 5-year progression-free survival (PFS), 5-year locoregional recurrence-free survival (LRFS), and relevant toxicities were analyzed. RESULTS: In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8-126 months). The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568). In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773) and 5-year LRFS (88.1% vs 90.8%, P=0.903). Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland) in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05). CONCLUSION: Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.

Expression of chemokine receptor CXCR4 is closely correlated with clinical outcome in human nasopharyngeal carcinoma.

The CXC chemokine receptor 4 (CXCR4) has been reported to be involved in the development and progression of nasopharyngeal carcinoma (NPC). However, the role of CXCR4 in clinical outcome and prognosis of NPC patients remains controversial. In the present study, we investigated and reviewed the expression of CXCR4 in NPC tissues and then analyzed the definitive role of CXCR4 in clinical outcome and prognosis. Here, we found that the expression level of CXCR4 was significantly higher in NPC cancer specimens (61/98) than that in paired non-tumor tissues (p < 0.001). Together with our pathological analysis, statistic analysis revealed that CXCR4 expression was indeed closely correlated with UICC stage (p = 0.000), N stage (p = 0.019), and metastasis (p = 0.000). Most importantly, the systematic review combined with our survival and multivariate analysis that revealed high expression of CXCR4 was obviously associated with poor overall survival (OS) (p = 0.000) and progression-free survival (PFS) (p = 0.000) and can act as an independent prognostic factor in NPC patients. In conclusion, this study suggests that CXCR4 is highly activated and expressed in the development of NPC and may be recommended as an indicator in the diagnosis of NPC. Thus, targeting of CXCR4 gene or protein could be used as a potential therapy for NPC.