Purpose: To investigate whether juvenile patients with nasopharyngeal carcinoma (NPC) in China have better prognosis than their adult counterparts in the intensity-modulated radiation therapy (IMRT) era, after controlling for potential confounding variables. Methods: Data pertaining to 1139 patients with newly diagnosed NPC without metastasis, who were treated with IMRT at our hospital, were retrospectively analyzed. Of these, 60 patients were juvenile (age <= 18 years) diagnosed between January 2003 and December 2018, while 1079 patients were adults (<= 65 years) diagnosed between January 2013 and December 2014. To minimize the influence of selection and confounding bias, 1:2 propensity score matching (PSM) was used. Overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method and between-group differences assessed using the Log rank test. The long-term toxicity of the juvenile patients was evaluated according to the criteria of the Radiation Therapy Oncology Group (RTOG) and the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: Five-year OS of juvenile and adult patients were 88.07% and 85.08%, respectively. Before PSM, OS, PFS, DMFS, or LRFS were comparable in the two groups (all P > 0.05). After PSM, OS, DFS, and LRFS in the juvenile group were markedly longer than that in adults (P = 0.005, P = 0.027, and P = 0.024, respectively). With respect to long-term toxicity, the most common adverse effects in juvenile patients were cervix fibrosis, ototoxicity, and xerostomia. However, except for two patients who developed grade 3 ototoxicity, all adverse effects were within grade 2. Conclusion: In the IMRT era, juvenile Chinese patients with NPC had better 5-year OS, DFS, and LRFS than their adult counterparts. The adverse events in the juvenile cohort were relatively mild; however, the risk of severe ototoxicity should not be neglected.

AMIGO2 (Adhesion molecule with Ig like domain 2) is a transmembrane adhesion protein, which is rich in 6 amino acid repeats. High AMIGO2 expression is closely related to gastric cancer, prostate cancer, oral cancer, cervical cancer and colon cancer. However, the role of AMIGO2 in the pathogenesis of nasopharyngeal carcinoma (NPC) has not been elucidated. The purpose of this study was to investigate the role and mechanism of AMIGO2 in NPC. mRNA expression in freshly frozen NPC (n = 10) and normal nasopharyngeal (n = 10) tissues (NP) was analyzed by qPCR. AMIGO2 expression in NPC cells and NP69 cell was quantified with qPCR assay and Western blotting, respectively. The CCK8 and colony formation assays were used to measure cell viability. Apoptosis was detected by cell flow cytometric. The cell wound healing, migration, and invasion assays were performed to evaluate the metastatic capacity in vitro. Lung metastasis model from tail vein in nude mice was evaluate the metastatic ability in vivo. In addition, Metastatic and EMT related makers were detected by Western blotting. Protein spectrum analysis (iTRAQ) was performed to evaluate the differential proteins and signaling pathways. Afterwards, the changes of MAKP signaling pathway were detected by Western blotting. It was found that the AMIGO2 mRNA expression in NPC tissues was significantly higher than that in normal NP tissues. Furthermore, the knockdown of AMIGO2 could inhibit proliferation, induce apoptosis, depress migration and invasion of NPC cells in vitro, and reduce the lung metastases of NPC cells in vivo. In addition, Western blotting revealed that knockdown of AMIGO2 results in an increase in the E-cadherin expression and a reduction in the Slug, N-cadherin, Vimentin, MMP2, and MMP9 expression. Mechanismally, the iTRAQ analysis showed that the MAPK signaling pathways were significantly regulated by the knockdown of AMIGO2 in NPC cell. Finally, Western blotting demonstrated that knockdown of AMIGO2 reduced the phosphorylation expression of p-MEK1/2, p-Erk1/2, p-c-Raf and the expression of c-fos, c-myc, MAPK6, PAK1, and MK5. AMIGO2 was demonstrated to promote NPC cell growth and metastasis by activating the MAPK signaling pathway. Our findings suggest that AMIGO2 is a potential therapeutic target for NPC.

To assess the changes in volume and spatial location of target area and surrounding organs during cone beam computed tomography (CBCT) for cervical cancer. Sixteen patients with cervical cancer were performed intensity-modulated radiation therapy using offline cone beam computed tomography (CBCT) weekly during chemo/radiation. CTV was contoured on the planning CT. Each CBCT was rigidly registered to the planning CT with respect to bony anatomy. A pelvic MRI scan was performed before the radiation therapy and during the radiation dose of 9Gy/5f, 18Gy/10f, 27Gy/15f, 36Gy/20f, and 48.6Gy/27f. Those MRI images were compared with the first CT image, respectively. Changes of the target volume and spatial location were analyzed and evaluated for each patient by volume difference method and DICE similarity method. The gross tumor volume (GTV-T) changed significantly from 79.62cm3 to 20.86cm3 (average 73.80%). The clinical target volume (CTV) changed slightly from 672.59 cm3 to 608.26cm3 (average 9.56%). The volume of Uterus (CTV-T) changed slightly from 83.72cm3 to 80.23cm3. GTV-T and CTV decreased gradually with the increase in the number of radiation, and the change of GTV-T was the most obvious. There was also significant difference in GTV-T and CTV-T among different groups (P<0.001), but CTV was not significantly different in volume (P>0.05) and the change of GTV-T had a linear correlation with the number of radiation therapy (P<0.001). The mean volume changed rate(delta V%) of GTV-T, CTV-T and CTV varied from 23.05%, 4.71% and 5.84% to 70.85%, 6.78% and 9.59%.There was significant difference in GTV-T among different groups (P<0.001),and the change of GTV-T had a linear correlation with the number of radiation therapy (P<0.001). There was a negative correlation between ¢V% and DSC in target area and organs at risk (r<0, P<0.05). The DICE similarity coefficient (DSC) of GTV-T decreased with the increase of fractions during the course of radiation therapy (P<0.001). There was significant difference between DSC5f and DSC15f, DSC20f or DSC27f (P<0.05), however, there was no significant difference between DSC5f and DSC10f (P>0.05). Significant variations in tumor regression and spatial location occurred during radiation therapy of cervical cancer. The volume change rate and DSC of GTV-T were all linear correlated with the increase of the number of radiation. Adaptive radiation therapy approaches are needed to improve the treatment accuracy for cervical cancer.

ObjectiveTo estimate whether a continuous infusion of intraperitoneal local anaesthetic for 48hours following laparoscopic hysterectomy reduced the need for opioids delivered with a patient-controlled analgesia pump.DesignDouble-blind randomised placebo-controlled trial.SettingDistrict general hospital in the UK.PopulationWomen undergoing a laparoscopic hysterectomy for a benign indication.MethodsWomen were randomised to receive either 0.5% levobupivicaine or 0.9% normal saline via an ON-Q elastomeric pump for 48hours postoperatively. The amount of opioids used via the patient-controlled analgesia pump was recorded and pain was measured using an 11-point Box Scale.Main outcome measuresThe primary outcome was the amount of patient-administered morphine used over the first 48 postoperative hours. Secondary outcomes were length of hospital stay, oral analgesia use and level of patient-reported pain.ResultsSixty women participated and completed the trial. There was no difference (P=0.59) in the median amount of patient-administered morphine used between the levobupivicaine (23mg) and placebo (18.5mg) groups; median group difference 3.0 (95% CI -7.0 to 14.0). There was also no difference in the length of hospital stay with 40% of the treatment group remaining in hospital >48hours compared with 30% of the placebo group (P=0.08). Pain scores at all postoperative time points remained similar, with a median group difference in pain scores of 1.0 (95% CI -1.0 to 2.0) at the end of the first postoperative day.ConclusionsContinuous infusion of 0.5% levobupivicaine into the peritoneal cavity following laparoscopic hysterectomy does not have any opioid-sparing effects.

To investigate the degree of tumor volume shrinkage during IMRT treatment for cervical cancer patient, and the benefit of a plan modification. Thirty-three cases of cervical cancer patients (stage IB-IIIB) with 7-field IMRT treatment were included in this study. They were treated between May 2011 and December 2012. The target dose was prescribed at 50.4 Gy/28 fractions. After patient was treated at 27-30.6 Gy, a new Helical CT (HCT) was scanned. The volume of target and organ-at-risk (OAR) were evaluated and a new plan would be performed and applied to the remaining fractions. The OARs included rectum, bladder and small intestine. The average volume of GTV from pre-treatment HCT and re-plan HCT was 74.9 ± 42.1 (range, 22.4-201.5) and 40.5 ± 22.2 cm3 (range, 7.5-120.4 cm3) respectively. The tumor volumes were reduced with 34.4 ± 31.3 cm3, or 41.9 ± 20.9% at the time of re-planning. For initial GTvs with volume <50 cm3, 50-80 cm3 and >80 cm3, the reductions were 32.4 ± 22.7%, 37.4 ± 14.0%, and 54.7 ± 19.7%, respectively. There was statistical significance (paired t-test, p = 0.019). The shrinkage is larger for large tumor. For the pre-treatment plans, D95 of PTV was 5024.5 ±65.8 cGy, V40 (OAR volume receiving ≥40 Gy) were 70.9 ± 12.9% and 74.1 ± 10.6% respectively for rectum and bladder, V35 of small intestine was 37.4 ± 17.0%. For the re-plans, D95 of PTV was 4993 ± 111.5 cGy, V40 were 69.8 ± 11.0% and 69.1 ± 9.2% for rectum and bladder, V35 of small intestine was 37.4 ± 17.0%. Tumor of Cervical cancer patients would shrink at 41.9 ± 20.9% in average at the middle of the treatment. A re-plan is necessary to reduce the irradiated volume, hence to reduce unnecessary radiation on surrounding normal structures.

To evaluate the performance of Atlas-based Autosegmentation with STAPLE algorithm for Head Neck cancer patient. Seven patients' planning CT images and the corresponding normal organ contours were selected from existed clinical HN cancer patient database based on the distribution of patient size and normal structure volume. All contours were carefully reviewed and modified by a senior physician before creating a template database for autosegmentation software. Auto segmentation was performed on the planning CT images of 15 extra HN patients using autosegmentation software with STAPLE segmentation algorithm. The same physician reviewed the auto generated contours and made necessary modification. The accuracy of auto segmentation was evaluated using the Dice Similarity Coefficient (DSC) and Mean Surface Distance (MSD) between contours generated by autosegmentation software and those modified by the physician. Seven normal organs, including Brain Stem, Cord, Right and Left Parotid, Mandible, Right and Left Submanidubular glands (SMG), were evaluated. Due to tumor invasion, 2 parotids and 8 SMG were excluded from the study. The average time of the auto-segmentation was 11 minutes per image. DSC and MSD are shown in the table. On an average, DSC is greater than 0.95 except for L_SMG (0.92). The major modification was for SMG due to the adjacent location of the tumor. For parotid, the main modification was at superior slices and skin area. For brain stem, the main modification was at two superior slices. Cord and Mandible need minor modification. The study demonstrated that STAPLE algorithm can be reliably applied for normal organ auto-segmentation of HN cancer patient. Minimal modification is needed to improve the auto-segmentation to the clinical accepted results.Poster Viewing Abstract 3565; TableContour SimilarityIndexBrainStemCordMandibleR_ParotidL_ParotidR_SMGL_SMGDSC0.96±0.020.99±0.020.99±0.010.95±0.050.95±0.030.95±0.030.92±0.07MSD(mm)0.34±0.220.06±0.090.05±0.050.60±0.550.65±0.430.38±0.260.51±0.55 Open table in a new tab