Colorectal cancer (CRC) is still the third most common cancer in the world with a limited prognosis due to the chemoresistance of CRC cells to 5‐fluorouracil (5‐FU)‐based chemotherapy. In our previous study, we revealed that miR‐204 overexpression could sensitize CRC cell to 5‐FU treatment through targeting HMGA2/PI3K signaling pathway; however, miR‐204 expression in CRC tissues is abnormally downregulated. Long non‐coding RNAs (lncRNAs) dysregulation has been reported in human diseases, including cancer. Also, lncRNA can regulate cancer cell proliferation, invasion, migration, as well as chemoresistance. LncRNA prostate cancer‐associated transcript 6 (PCAT6) acts as an oncogene in many cancers; herein, PCAT6 expression was abnormally upregulated in CRC tissues and cell lines, suggesting its potential role in CRC. Further, we assessed the specific function and mechanism of PCAT6 in CRC. Furthermore, we revealed that PCAT6 knockdown attenuated CRC chemoresistance to 5‐FU through miR‐204/HMGA2/PI3K; miR‐204 inhibition could partially reverse the effect of PCAT6 knockdown. Taken together, we demonstrate that the abnormal PCAT6 overexpression inhibits miR‐204 expression in CRC, thereby promoting HMGA2/PI3K signaling activity, ultimately enhancing the chemoresistance of CRC cells to 5‐FU; PCAT6 represents a promising target for dealing with CRC chemoresistance.

ObjectiveTo retrospectively analyze the prognostic value of magnetic resonance imaging (MRI)-derived residual tumors after intensity-modulated radiation therapy (IMRT) in the patients with locally-advanced nasopharyngeal carcinoma.MethodsA total of 358 patients with locally-advanced nasopharyngeal carcinoma who received IMRT were classified as having residual tumors or no residual tumor based on MRI at the end of radiotherapy. The χ2 test, log-rank test, Cox proportional hazards regression model and Kaplan-Meir survival curves were used to investigate the relationship of clinicopathological features and residual tumors and to assess the prognostic value of residual tumors.ResultsThe 3-year overall survival (OS) rate was 73% in the residual tumor group and 90% in the no residual tumor group (HR 2.15, 95% CI 1.21-3.82,, P = 0.007); 3-year local relapse-free survival (LRFS) was 89% in the residual tumor group and 97% in the no residual tumor group (HR 4.46, 95% CI 1.61-12.38, P = 0.002); 3-year disease free survival (DFS) was 67% in the residual tumor group and 82% in the no residual tumor group (HR 2.21, 95% CI 1.40-3.48, P = 0.001). A high prescribed radiation dose (>73.92 Gy) did not increase the percentage volume of the GTVnx receiving 95% of the prescribed dose (GTVnx V95%) or improve any survival outcome.ConclusionThe presence of a residual tumor after IMRT was a significant negative independent prognostic factor for OS, LRFS and DFS. Although IMRT have improved the distribution of radiotherapy doses into the tumors, residual tumors detected by MRI after IMRT are still associated with poor prognosis in patients with advanced nasopharyngeal carcinoma.

Purpose To compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in treating early T-stage nasopharyngeal carcinoma (NPC). Method Ten patients with early T-stage NPC who received tomotherapy using simultaneously integrated boost (SIB) strategies were replanned with VMAT (RapidArc of Varian, dual-arc). Dosimetric comparisons between the RapidArc plan and the HT plan included the following: (1) D98, homogeneity, and conformity of PTVs; (2) sparing of organs at risk (OARs); (3) delivery time and monitor units (MUs). Results (1) Compared with RapidArc, HT achieved better dose conformity (CI of PGTVnx + nd: 0.861 versus 0.818, P = 0.004). (2) In terms of OAR protection, RapidArc exhibited significant superiority in sparing ipsilateral optic nerve (Dmax: 27.5Gy versus 49.1Gy, P < 0.001; D2: 23.5Gy versus 48.2Gy, P < 0.001), contralateral optic nerve (Dmax: 30.4Gy versus 49.2Gy, P < 0.001; D2: 26.2Gy versus 48.1Gy, P < 0.001), and optic chiasm (Dmax: 32.8Gy versus 48.3Gy, P < 0.001; D2: 30Gy versus 47.6Gy, P < 0.001). HT demonstrated a superior ability to protect the brain stem (D1cc: 43.0Gy versus 45.2Gy, P = 0.012), ipsilateral temporal lobe (Dmax 64.5Gy versus 66.4 Gy, P = 0.015), contralateral temporal lobe (Dmax: 62.8Gy versus 65.1Gy, P = 0.001), ipsilateral lens (Dmax: 4.27Gy versus 5.24Gy, P = 0.009; D2: 4.00Gy versus 5.05Gy, P = 0.002; Dmean: 2.99Gy versus 4.31Gy, P < 0.001), contralateral lens (Dmax: 4.25Gy versus 5.09Gy, P = 0.047; D2: 3.91Gy versus 4.92Gy, P = 0.005; Dmean: 2.91Gy versus 4.18Gy, P < 0.001), ipsilateral parotid (Dmean: 36.4Gy versus 41.1Gy, P = 0.002; V30Gy: 54.8% versus 70.4%, P = 0.009), and contralateral parotid (Dmean: 33.4Gy versus 39.1Gy, P < 0.001; V30Gy: 48.2% versus 67.3%, P = 0.005). There were no statistically significant differences in spinal cord or pituitary protection between the RapidArc plan and the HT plan. (3) RapidArc achieved a much shorter delivery time (3.8 min versus 7.5 min, P < 0.001) and a lower MU (618MUs versus 5646MUs, P < 0.001). Conclusion Our results show that RapidArc and HT are comparable in D98, dose homogeneity, and protection of the spinal cord and pituitary gland. RapidArc performs better in shortening delivery time, lowering MUs, and sparing the optic nerve and optic chiasm. HT is superior in dose conformity and protection of the brain stem, temporal lobe, lens, and parotid.

BackgroundBrainstem dose limitations influence radiation dose reaching to tumor in the patients with locally-advanced nasopharyngeal cancer (NPC).MethodsA retrospective analysis of the prognostic value of the distance between the primary tumor and brainstem (Dbs) in 358 patients with locally-advanced NPC after intensity-modulated radiation therapy (IMRT). Receiver operating characteristic (ROC) curves were used to identify the cut-off value to analyze the impact of Dbs on tumor dose coverage and prognosis.ResultsThe three-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were 88.8 vs. 78.4 % (P = 0.007), 96.5 vs. 91.1 % (P = 0.018), 87.8 vs. 79.3 % (P = 0.067), and 84.1 vs. 69.6 % (P = 0.002) for the patients with the Dbs > 4.7 vs. ≤ 4.7 mm, respectively. ROC curves revealed Dbs (4.7 mm) combined with American Joint Committee on Cancer (AJCC) T classification had a significantly better prognostic value for OS (P < 0.05).ConclusionsDbs (≤4.7 mm) is an independent negative prognostic factor for OS/LRFS/DFS and enhances the prognostic value of T classification in the patients with locally-advanced NPC.

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