Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003–2013 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized. METHODS AND MATERIALS: Consecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival. RESULTS: Of the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and >5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (≥50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival. CONCLUSION: This large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.

Proposal of a Pretreatment Nomogram for Predicting Local Recurrence after Intensity-Modulated Radiation Therapy in T4 Nasopharyngeal Carcinoma: A Retrospective Review of 415 Chinese Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Local relapse-free survival (LRFS) differs widely among patients with T4 category nasopharyngeal carcinoma (NPC). We aimed to build a nomogram incorporating clinicopathological information to predict LRFS in T4 NPC after definitive intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: Retrospective study of 415 Chinese patients with non-metastatic T4 NPC treated with definitive IMRT with or without chemotherapy at our cancer center between October 2009 and September 2013. The nomogram for LRFS at 3 and 5 years was generated based on multivariate Cox proportional hazards regression, and validated using bootstrap resampling, assessing discriminative performance using the concordance index (C-index) and determining calibration ability via calibration curves. RESULTS: Five-year LRFS was 88.8%. We identified and incorporated four independent prognostic factors for LRFS: ethmoid sinus invasion, primary gross tumor volume, age, and pretreatment body mass index. The C-index of the nomogram for local recurrence was 0.732 (95% confidence interval, 0.726 to 0.738), indicating excellent predictive accuracy. The calibration curve revealed excellent agreement between nomogram-predicted and observed LRFS probabilities. Risk subgroups based on total point score cutoff values enabled effective discrimination of LRFS. CONCLUSION: This pretreatment nomogram enables clinicians to accurately predict LRFS in T4 NPC after definitive IMRT, and could help to facilitate personalized patient counselling and treatment strategies.

Dosimetric benefit to organs at risk following margin reductions in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy / 癌症

<p><b>INTRODUCTION</b>It is important to decrease the radiation exposure of normal tissue in intensity-modulated radiation therapy (IMRT). Minimizing planning target volume (PTV) margins with more precise target localization techniques can achieve this goal. This study aimed to quantify the extent to which organs at risk (OARs) are spared when using reduced margins in the treatment of nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>Two IMRT plans were regenerated for 40 patients with NPC based on two PTV margins, which were reduced or unchanged following cone beam computed tomography online correction. The reduced-margin plan was optimized based on maximal dose reduction to OARs without compromising target coverage. Dosimetric comparisons were evaluated in terms of target coverage and OAR sparing.</p><p><b>RESULTS</b>Improvements in target coverage occurred with margin reduction, and significant improvements in dosimetric parameters were observed for all OARs (P < 0.05) except for the right optic nerve, chiasm, and lens. Doses to OARs decreased at a rate of 1.5% to 7.7%. Sparing of the left parotid and right parotid, where the mean dose (Dmean) decreased at a rate of 7.1% and 7.7%, respectively, was greater than the sparing of other OARs.</p><p><b>CONCLUSIONS</b>Significant improvements in OAR sparing were observed with margin reduction, in addition to improvement in target coverage. The parotids benefited most from the online imaging-guided approach.</p>

A novel full-length gene of human ribosomal protein L14.22 related to human glioma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This study was undertaken to obtain differentially expressed genes related to human glioma by cDNA microarray and the characterization of a novel full-length gene.</p><p><b>METHODS</b>Total RNA was extracted form human glioma and normal brain tissue, and mRNA was used as a probe. The results of hybridization procedure were scanned with the computer system. The gene named 507E08 cone was subsequently analyzed by northern blot, bioinformatic approach, and protein expression.</p><p><b>RESULTS</b>Fifteen differentially expressed genes were obtained from human glioma by hybridization and scanning for four times. Northern blot analysis confirmed that the 507E08 clone was low expressed in human brain tissue and over expressed in human glioma tissues. The analysis of BLASTn and BLASTx showed that the 507E08 clone was a novel full-length gene, which codes 203 amino acid of protein and is called human ribosomal protein 14.22 gene. The nucleotide sequence had been submitted to the GenBank with the accession number of AF329277. After expression in E. coli., protein yielded a major band of apparent molecular mass 22 kDa on an SDS-PAGE gel.</p><p><b>CONCLUSIONS</b>cDNA microarray technology can be successfully used to identify differentially expressed genes. The novel full-length gene of human ribosomal protein 13.22 may be correlated with the development of human glioma.</p>

cDNA microarray in isolation of novel differentially expressed genes related to human glioma and clone of a novel full-length gene / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This investigation was undertaken to obtain differentially expressed genes related to human glioma using cDNA microarray and the characterization of one novel full-length gene.</p><p><b>METHODS</b>Total RNA was extracted from human glioma tissues and normal brain tissues, and mRNA was used to make probes. After hybridization and washing, the results were scanned using a computer system. The gene named 681F05 clone was an expressed gene to human glioma through four-time hybridization and scanning. Subsequently northern blot analysis was performed by northern blot, 5'RACE and bioinformatics.</p><p><b>RESULTS</b>Fifteen differentially expressed genes to human glioma were obtained through four-time hybridization and scanning. Northern blot analysis confirmed that 681F05 clone was low-expressed in human brain tissues and over-expressed in human glioma tissues. The analysis of BLASTn and BLASTx showed that 681F05 clone is two cDNA clones encoding two novel proteins that are highly identified to the cyclophilin isoform 10 of C. Elgans, respectively. Sequence analysis revealed the two cDNA clones are two different splicing variants of a novel cycophilin-like gene (PPIL3a and PPIL3b).</p><p><b>CONCLUSIONS</b>cDNA microarray technology can be successfully used to identify differentially expressed genes. The novel full-length gene of human PPIL3 may be correlated with the formation of human glioma.</p>

A new metallic oxide semiconductor field effect transistor detector for use of in vivo dosimetry / 中华放射肿瘤学杂志

To investigate the application of a recently developed metallic oxide semiconductor field effect transistor(MOSFET)detector for use in vivo desimetry.Methods The MOSFET detector was calibrated for X-ray beams of 8 MV and 15 MV,as well as electron beams with energy of 6,8,12 and 18 MeV.The dose linearity of the MOSFET detector was investigated for the doses ranging from 0 up to 50 Gy using 8 MV X-ray beams.Angular effect was evaluated as well in a cylindrical PMMA phantom by changing the beam entrance angle every 15?clockwise.The MOSFET detector was then used for a breast cancer patient in vivo dose measurement, after the treatment plan was verified in a water phantom using a NE-2571 ion chamber,in vivo measurements were performed in the first and last treatment,and once per week during the whole treatment.The measured doses were then compared with planning dose to evaluate the accuracy of each treatment.Results The MOSFET detector represented a good energy response for X-ray beams of 8 MV and 15 MV,and for electron beams with energy of 6 MeV up to 18 MeV.With the 6 V bias,Dose linearity error of the MOSFET detector was within 3.0% up to approximately 50 Gy,which can be significantly reduced to 1% when the detector was calibrated before and after each measdurement.The MOSFET response varied within 1.5% for angles firm 270?to 90?.However,maximum error of 10.0% was recorded comparing MOSFET response between forward and backward direction.In vivo mea surement for a breast cancer patient using 3DCRT showed that,the average dose.deviation between measurement and calculation was 2.8%,and the maximum error was less then 5.0%.Conclusions The new MOSFET detector,with its advantages of being in size,easy use,good energy response and dose linearity,can be used for in vivo dose measurement.