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Objective:To evaluate the diagnostic value of HPV detection in squamous cell carcinoma of the cervical lymph node metastasis from an unknown primary site.Methods:Clinical data of 6 patients who were initially diagnosed with squamous cell carcinoma of the cervical lymph node metastasis from an unknown primary site and eventually diagnosed with HPV-related oropharyngeal squamous cell carcinoma were collected, and the process of diagnosis was analyzed.Results:Upon the initial admission, all patients were diagnosed with squamous cell carcinoma of the cervical lymph node metastasis with positive p16 expression, positive HPV-16 subtype and negative EBER expression. No obvious primary lesion was found after comprehensive examination. Subsequently, four of them underwent ipsilateral tonsollar blind biopsy ( n=2) and ipsilateral tonsillectomy ( n=2). All these four patients were pathologically diagnosed with tonsillar squamous cell carcinoma. For the other two cases, MRI detected the thickening complicated with enhancement of ipsilateral wall of oropharynx and tongue root after follow-up for D149 and D545 , respectively. Biopsy confirmed the diagnosis of squamous cell carcinoma of the tonsil and tongue root, respectively. Conclusion:For patients with HPV-positive squamous cell carcinoma of the cervical lymph node metastasis from an unknown primary site, the possibility that the primary lesion originates from the oropharyngeal site, especially the tonsil and tongue root, should be highly suspected.
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The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer is growing year by year. Compared with the other head and neck squamous cell carcinoma, HPV-positive oropharyngeal cancer has unique biological characteristics and better prognosis. According to the 8 th edition TNM staging of UICC/AJCC, HPV-positive and HPV-negative oropharyngeal cancer have been classified separately. In 2018, College of American Pathologists and American Society of Clinical Oncology released the guidelines on the HPV testing in head and neck cancer. Several published clinical trials have demonstrated that de-intensified chemoradiation might be efficacious treatment of HPV-positive oropharyngeal cancer.
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Objective@#To study the effect of microgroove surface modification of titanium and zirconia on the biological behavior of gingival fibroblasts in order to find suitable surface materials for the transmucosal part of the dental implant.@*Methods@#Twenty specimens were divided into four groups: smooth titanium (Ti-S), smooth zirconia (ZC-S), microgroove titanium (Ti-MG) and microgroove zirconia (ZC-MG) (five specimens in each group). Microgroove modification of titanium and zirconia surfaces was carried out by using fine machining chip system in the last two groups. The width of groove ridge was 60 μm, the width of groove was 60 μm, the depth of groove was 10 μm. The surface morphologies (the groove width and depth) were observed by scanning electron microscope (SEM), the surface roughness, static contact angle and elemental of specimens in each group were detected by SEM, atomic force microscope (AFM), optical contact angle measuring device and energy-dispersion X-ray analysis (EDX). Morphology of human gingival fibroblast (HGF) that arranged along the groove was analyzed using laser scanning confocal microscope by immunofluorescence staining. Differences in cell proliferation were analyzed and compared using cell counting kit. Expression level of intergrin α5, β1 and collagen Ⅰ mRNA were compared among different groups by quantitative real-time PCR for 6 h and 3 d.@*Results@#The surface roughness of smooth titanium group and smooth zirconia group was (63.23± 2.55) and (26.78±3.11) nm, respectively. Microgroove zirconia group showed the best hydrophilicity: the static contact angle was 51.2°±2.0°. HGF was arranged along the groove surface, and cell proliferation results showed that proliferation on microgroove zirconia was more significant than that on other groups from 6 h to 7 d (P<0.05). Intergrin α5 mRNA has the highest expression in microgroove zirconia (P<0.05) in the early adhesion (6 h), and there was no significant difference in the surface expression of intergrin β1 and collagen Ⅰ mRNA in the early adhesion (6 h) of each group. However, in the late adhesion (3 d), intergrin α5, β1 and collagenⅠ mRNA expression in microgroove surface groups were higher than those of the smooth groups (P<0.05).@*Conclusions@#Microgroove zirconia surface has small roughness and good hydrophilicity, which can guide HGF to line up in the groove, and this is beneficial to the HGF proliferation and the expression of structural proteins and functional proteins.
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Objective To compare the effect between the supine and prone patient positions upon target dose coverage during intensity-modulated radiotherapy (IMRT) for rectal cancer, aiming to provide clinical reference for the selection of position for rectal cancer patients. Methods Twenty-four patients diagnosed with rectal cancer receiving postoperative adjuvant radiotherapy were selected and divided into the supine (n=12) and prone position groups(n=12). Before and during the IMRT(1-4 weeks),all patients received CT scans, which were defined as:Plan,1W,2W,3W and 4W,respectively. The organs at risk were delineated based on CT scan images. Plan,1W, 2W, 3W and 4W CT scan images were fused. The CTV and PTV from Plan CT scan were copied to the 1-4W CT scan images,and the therapeutic plans from Plan CT scan were copied as well. The target dose coverage was assessed and the failure rate of target dose coverage was calculated. The couch-position data for each patient during each cycle of IMRT were recorded by using the MOSAIQ network and the overall deviation (S) of couch position was calculated. Results The failure rates of CTV and PTV target dose coverage in the prone position group were higher than those in the supine position group (18.60% VS 0%, 69.76% VS 53.65%).The S value was significantly correlated with the target dose coverage (r=-0.683,P=0.000). The S value in the prone position group was(1.23±0.76) cm,significantly greater than(0.28±0.18) cm in the supine position (P=0.001),and the most significant deviation was noted in the y (head and foot) and z (frontal and dorsal) directions (P=0.003 and 0.003). Compared with the supine group,the V5and V10 of the small intestine were significantly less (P=0.003 and 0.004) and the chronic toxicity (NTCPC) was considerably reduced(P=0.041) in the prone position group. Conclusions A better target dose coverage can be maintained during IMRT with a supine position during rectal cancer IMRT, whereas the positioning repeatability is worsened with a prone position due to use of the belly board, thereby affecting the target dose coverage. Although the prone position combined with belly board can reduce the tolerated dosage of the small intestine,effective measures should be taken to guarantee the patient positioning repeatability.
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Emerging clinical evidence revealed that postoperative adjuvant chemoradiotherapy (CRT) could improve the clinical outcome for resected head and neck squamous cell carcinoma in high-risk patients. The irradiation targets and doses should be determined by the primary tumor site, clinical stage, pathology reports, and the evaluation of postoperative imaging. Adjuvant concurrent CRT with cisplatin is the current standard treatment for high-risk postoperative head and neck squamous cell carcinoma patients. However, the effect of concurrent CRT with other chemotherapeutic agents and (or) epidermal growth factor receptor (EGFR) monoclonal antibody in these patients is inconclusive. Human papillomavirus (HPV)-positive oropharyngeal cancer has the unique biological characteristics, and the indications and treatment models of postoperative adjuvant CRT for these patients are still unclear. Further study is needed.
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Objective To study three contouring approaches of the bowel and evaluate the bowel dose volume with cervical cancer patient.Methods Twelve patients were selected,prescribed dose 45 Gy/ 25f.For each patient we contoured the bowel according to three different definitions:bowel loops,bowel bag and peritoneal space.Then we generated three rival plans each considering a different bowel definition and to evaluate dose differences of the HI,CI of PTV and D D V5-V45 of bowel loops with paired t-test.Results Comparison between BL and BB plan,Dmax,HI and CI of PTV,V5-V45 of bowel loops were not significantly different (P =0.171,0.076,0.192,P =0.315-0.855),D of PTV and Dmax of bowel loops had difference (P=0.017,0.038).Comparison between BL and PS plan,Dmax,D HI and CI of PTV and Dmax of bowel loops had differences (P=0.033,0.044,0.046,0.041,0.013),V5-V45 of bowel loops were not significantly different (P=0.416-0.977).If the bowel loops V40 ≤ 15%,and bowel bag and peritoneal space V40≤20%.Conclusions All definitions provided a very similar dose volume of bowel loops.Taking into account HI and CI of PTV and max dose of bowel loops,BB seems better than PS.
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Objective To investigate the difference in normal tissue complication probability (NTCP) of lower cranial nerves (LCNs) between target volumes recommended by Radiation Therapy Oncology Group (RTOG) and China in intensity-modulated radiotherapy (IMRT) for T1-2 nasopharyngeal carcinoma (NPC),and to provide the evidence of dose-volume effect for the protection of LCNs in IMRT for NPC.Methods A total of 20 patients with T1-2 NPC who were treated from 2013 to 2015 were enrolled,and LCNs were delineated on CT images.Target volume delineation and treatment plan designing were performed according to the method recommended by RTOG0225 (RTOG target volume delineation method) or the Chinese Working Committee for Clinical Staging of NPC in 2010 (Chinese target volume delineation method),and the differences in the dose to LCNs and NTCP were calculated.Results In the RTOG and Chinese methods for target volume delineation,Dmax to the left and right LCNs was 7 450±273 cGy/7294±309 cGy and 7 361± 160 cGy/7 190±395 cGy,respectively (P=0.018 and 0.042),Dmean was 6735±285 cGy/6 660±333 cGy and 6 446±429 cGy/6 299±467 cGy,respectively (both P=0.000),and the NTCP was 60%±10%/57%±13% and 51%±15%/45%±17%,respectively (both P=0.000).Conclusions It is feasible to precisely delineate target volume with the LCNs as a routine OAR and predict NTCP in IMRT for T1-2 NPC.The NTCP of the LCNs is closely associated with target volume dose and irradiated volume.The dose to the LCNs and NTCP determined by the Chinese target volume delineation method are significantly lower than those determined by the RTOG method.
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To determine the clinical effect of Radiofrequency Ablation [RFA] for residual lung metastases from breast cancer after systemic chemotherapy. An experimental study. The Second Affiliated Hospital of Soochow University, Suzhou, Fudan University Shanghai Cancer Center, Shanghai, China, from January 2008 to October 2014. Thirty-five breast cancer patients with 67 pulmonary metastases were involved in this study. All lesions were treated by RFA and followed by CT-scan. Primary endpoint of this clinical study was local control; secondary endpoints were overall survival and treatment-related toxicities. Complete Response [CR] was observed in 59 lesions, with Partial Response [PR] in 4 lesions, Stable Disease [SD] in 1 lesion and Progression Disease [PD] in 3 lesions. The lesion diameter > 2 cm was related to poor local control [p=0.04]. The median Overall Survival [OS] was 33 months [95%CI: 21.6 - 44.4]. One-, 2-, and 3-year OS rates were 88.6%, 59.3% and 42.8% respectively. The mumber of pulmonary metastases [>/= 2], the diameter of lesion [> 2 cm] and coexisting with liver metastases were significantly correlated to poor OS by multivariate analysis. Log-rank test showed statistically significant difference of OS in diameter of lesion and coexisting with other metastases. RFA is a promising treatment option for patients with residual lung metastases from breast cancer after systemic chemotherapy in selected patients
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Objective To study the appropriate neck irradiation volume for neck lymph nodenegative nasopharyngeal carcinoma patients by Meta-analysis.Methods The related references published from Jan 1990 to Jun 2013 were searched in Pubmed,Embase,Cochrane and Wangfang Databases.The qualified references for enrollment criteria were screened and the relative data were collected.The OR (Odds ratio) value by fixed effect model was used to evaluate the data for patients who received radiotherapy between the upper neck and whole neck irradiation.The endpoints including 5-year neck local control rate (LCR),neck-in-irradiation LCR,and neck-outsides-irradiation LCR.Results Five qualified references were screened and belonged to respective research.There enrolled 1 333 patients,including 970 patients who received the upper neck irradiation and 363 patients who received the whole neck irradiation,respectively.The forest plots revealed that there were no significant differences for 5-year neck LCR,neckin-irradiation LCR,and neck-outsides-irradiation LCR for patients received radiotherapy between the upper neck and whole neck irradiation.These OR values were 0.89 (95% CI:0.41-1.94),1.29 (95% CI:0.58-2.88) and 0.42 (95% CI:0.07-2.36),respectively.Conclusions The Meta-analysis results suggest that irradiation to the upper neck for neck lymph node-negative nasopharyngeal carcinoma can be appropriate.
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Objective To assess the differences in delineation of organs at risk (OAR) and dosimetry between junior and senior physicians during intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) and to evaluate the role of specific training in reducing the differences.Methods Sixteen patients newly diagnosed with NPC were selected in the study.The OAR was delineated separately by three junior physicians and three senior physicians,and the geometric and dosimetric differences were assessed relative to the reference OAR.Delineation was performed again for the two OARs with the biggest difference after specific training in the two groups of physicians,and the differences were evaluated again.The difference was determined by paired t test.Results The maximum dose differences (Dmax) of OAR in the junior and senior physicians were (2.33 ± 12.06) % (-48.06%-137.82%) and (0.09 ± 4.72) % (-49.54%-42.96%),respectively (P =0.039),and the difference in the optic chiasm was the greatest ((5.85 ± 19.63) % ∶ (1.36 ± 4.64) %,P =0.042).The mean dose differences (Dmean) of OAR in the junior and senior physicians were (3.10 ± 8.07)% (-46.76%-59.76%) and (-0.93 ± 2.03) % (-45.54%-35.69%),respectively (P =0.021),and the difference in the parotid gland was the greatest ((13.23 ± 13.39) % ∶ (3.20 ± 6.71) %,P =0.002).In the secondary delineation after training,the Dmax of the optic chiasm in the junior and senior physicians was (1.68 ± 3.34)% and (1.50 ± 1.87) %,respectively (P =0.841),and the difference in junior physicians was reduced significantly compared with before training ((1.68 ± 3.34) % ∶ (5.85 ± 19.63) %,P =0.048) ; the Dmean of the parotid gland in the junior and senior physicians was (2.46 ± 3.06) % and (1.35 ± 3.00) %,respectively (P =0.2 7 4),significantly reduced compared with before training ((2.46 ± 3.0 6) % ∶ (13.23 ± 13.39)%,P=0.002; (1.35 ± 3.00)% ∶ (3.20 ± 6.71) %,P =0.033).Conclusions The differences in delineation of OAR lead to dose uncertainties during IMRT for NPC,and specific training can improve the accuracy of delineation.
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Objective To investigate the effect of human lung cancer-associated fibroblasts (CAF) on the radiosensitivity of lung cancer cells when CAF is placed in direct contact co-culture with lung cancer cells.Methods Human lung CAF was obtained from fresh human lung adenocarcinoma tissue specimens by primary culture and subculture and was then identified by immunofluorescence staining.The CAF was placed in direct contact co-culture with lung cancer A549 and H1299 cells,and the effects of CAF on the radiosensitivity of A549 and H1299 cells were evaluated by colony-forming assay.Results The human lung CAF obtained by adherent culture could stably grow and proliferate,and it had specific expression of α-smooth muscle actin,vimentin,and fibroblast activation protein,but without expression of cytokeratin-18.The plating efficiency (PE,%) of A549 cells at 0 Gy irradiation was (20.0 ± 3.9) % when cultured alone versus (32.3 ± 5.5) % when co-cultured with CAF (t =3.16,P < 0.05),and the PE of H1299 cells at 0 Gy irradiation was (20.6 ± 3.1) % when cultured alone versus (35.2 ± 2.3) % when co-cultured with CAF (t =6.55,P <0.05).The cell survival rate at 2 Gy irradiation (SF2) of A549 cells was 0.727 ±0.061 when cultured alone versus 0.782 ± 0.089 when co-cultured with CAF (t =0.88,P > 0.05),and the SF2 of H1299 cells was 0.692 ±0.065 when cultured alone versus 0.782 ± 0.037 when co-cultured with CAF (t =2.08,P >0.05).The protection enhancement ratios of human lung CAF for A549 cells and H1299 cells were 1.29 and 1.25,respectively.Conclusions Human lung CAF reduces the radiosensitivity of lung cancer cells when placed in direct contact co-culture with them,and the radioprotective effect may be attributed to CAF promoting the proliferation of lung cancer cells.
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Objective To investigate the dosimetric difference of organ at risk (OAR) for planning and actual estimated during intensity-modulated radiotherapy (IMRT) for patients with nasopharyngeal carcinoma.Methods Thirteen patients were enrolled to accept full course of IMRT.CT scans were acquired in the 10th,20th,and 30th fractions during radiotherapy,respectively.OAR,including brain stem,spinal cord,parotid gland and submandibular gland,were delineated on repeated CT scans.The volume change of OAR were investigated.After that,the plans were copied to the new CT image to calculate the escalated average dose of OAR during radiotherapy (Actual estimated receiving dose minus planning dose).Results The change trend of volume was decreasing gradually for parotid gland and submandibular gland during the 10th,20th,and 30th times radiotherapy (all P =0.000).The maximum dose (Dmax) of brain stem and spinal cord and the 50% volume receiving dose (D50) of parotid gland increased significantly in the 10th,20th,and 30th times during radiotherapy,respectively.The escalated average dose were 3.76 and 3.68 Gy for Dmax of brain stem and spinal cord (P =0.000,0.000),5.11 and 3.54 Gy for D50 of left and right parotid (P =0.001,0.023),and 0.49 and 0.75 Gy for D50 of left and right submandibular gland (P =0.220,0.230),respectively.Conclusions The volume of parotid gland and submandibular gland significantly decreased after radiotherapy The actual receiving dose of brain stem,spinal cord,and parotid gland increased significantly during radiotherapy.However,there was no significant change for the actual receiving dose of submandibular gland.
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Objective To compare the agreement among Chinese 1992, 2008 and UICC 2010 staging systems of nasopharyngeal carcinoma (NPC) and evaluate their predictive value of radiotherapeutic prognosis.Methods 347 NPC patients without distant metastasis treated in our hospital from 2000 to 2005 were retrospectively analyzed.Every patient was categorized into T, N, and clinical stage by Chinese 1992, 2008 and UICC 2010 staging systems, respectively.Kappa value was used to evaluate the agreement among three systems.Kaplan-Meier method was used to analyze the 5-year overall survival (OS), local-free survival (LFS) and distant metastasis-free survival (DMFS), the difference between subgroup was tested by Logrank.Results The agreement of clinical stage, T and N stage between Chinese 2008 and UICC 2010 staging system was better than that of them compared to 1992 staging system, Kappa value were 0.700、0.881 and 0.722.The agreement of T stage was better than N and clinical stage among these three staging system.The difference of OS between stageⅢ and stage Ⅳ was significant in Chinese 2008 and UICC 2010 staging system (χ2=4.48,P=0.034;χ2=8.88,P=0.003), and with no different in 1992 staging system (χ2=0.40,P=0.526).There was no significant difference of LFS between T1 and T2,T2 and T3,T3 and T4 in all staging systems (χ2=1.85,0.53,0.50,P=0.174,0.467,0.479;χ2=1.25,2.10,1.99,P=0.264,0.148,0.159;χ2=0.77,0.60,0.87, P=0.381,0.441,0.350).There were no significant differencesin 1992 staging system, while there was significant differences of DMFS between N1 and N2, N2 and N3 in 2008 stage system, N1 and N2 in UICC 2010 stage system.Conclusions The predictive value of Chinese 2008 and UICC 2010 staging system for prognosis were similar, and were better than that of 1992 staging system in NPC.
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Objective To investigate the changes of target during fractionated radiotherapy for e-sophageal cancer, and to assess their impact on the implementation of radiotherapy. Methods Fourteen pa-tients with unresectable esophageal cancer were enrolled to receive full course conformal radiotherapy. CT scans were performed after every ten fractions. New targets (GTV) were delineated on repeated CT scans. Then the pretreatment radiotherapy plans were copied to the new targets to investigate the conformity between the new GTV and the plans. Results The majority of the GTVs decreased with the increasing fractions dur-ing radiotherapy. However, GTVs of 35.7% (5/14) patients increased by 2.0%-37.7% at the tenth frac-tion. The PTVs covered by 95% isodose curve at the time of pretreatment,tenth fraction,twentieth fraction and thirtieth fraction were 97.81%±1.53%, 91.95%±5.25%, 94.27%±4.23% and 94.03%±6.45%, respectively. Moreover, at tenth, twentieth and thirtieth fraction, there were 6,5, and 4 patients whose PTVs covered by 95% isodose curve were below 95%, respectively. Conclusions There are signifi-cant target changes during fractionated radiotherapy for esophageal cancer, which may result in uncertainties of radiotherapy implementation.
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Microenviroment hypoxia is one of the common phenomenon in cancer,studies have indiacat-ed that hypoxia induces genetic instability via activating many DNA danlage-repair signal pathways,which asso-ciates with tumor invasion and resistance and chemi-radiotherapy resistivity.Here,we overview three main DNA damage-repair pathways:mismatch repair,homologous recombination and non-homologous end joining,and how hypoxia influences their mechanisms.
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(0.05)). Multivariate analysis revealed that adjuvant radiotherapy and histology of tumor significantly affected the prognosis(P=(0.045) and P=(0.009), respectively). Whereas loco-regional control was only significantly affected by adjuvant radiotherapy(P=(0.000)). CONCLUSION: Adjuvant radiotherapy and histology of tumor are the important prognostic factors in the rectal cancer patients after treatment with multimodality therapy based on surgery.
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Patients with ataxia-telangiectasia ( A-T) syndrome were charachaterized by profound hypersensitivity to ionizing radiation in clinic. Many studies have shown that this hypersensitivity possibly attributed to ATM gene whose critical compartment was ATM kinase. So inhibitors of the ATM kinase such as caffeine, pentoxifylline, methyl xanthines and 7-hydroxystaurosporine (UCN-01) were developed and have achieved a few encouraging results in basic and clinical stuides.
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Objective To define the correlation between mutation of DNA-LigaseⅣ gene and radiosensitivity.Methods Nasopharyngeal squamous carcinoma cell line (CNE), lung adenocarcinoma cell line (SPC-A1) and breast adenocarcinoma cell line(MCF-7) after irradiation were assessed with specific biological parameters. Polymerase chain reaction, cloning and sequencing techniques were used to determine the sequence of DNA-LigaseⅣ gene in these three cell lines. Then the impact of homologous change and mutation on hydrophicity-hydrophobicity of genic products was analyzed.Results The surviving fractions derived from irradiation were different with more radiosensitivity in the CNE cell line than in the others. In three cell lines, the homology of LigaseⅣ gene were: 99.95%,99.99%,99.98%, respectively. Some mutations including transversion and transition were detected and led to alterations in the hydrophicity-hydrophobicity function of products. Higher radiosensitivity of CNE was associated with amino-acid substitutions: 313aa His→Arg,538aa Gly→Arg,579aa Lys→Arg and 585aa Asn→Ser.Conclusion These results suggest that LigaseⅣp play an important role in the ligation of DNA double strand breaks and certain mutations bring about changes in radiosensitivity.
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Objective To investigate the change in mRNA expression of hypoxia inducible factor 1? HIF 1? and vascular endothelial growth factor (VEGF) genes in the highly differentiated nasopharyngeal squamous carcinoma (CNE) cell line during hypoxia reoxygenation.Methods CNE cells were cultured in normoxic, continuous 8 hour hypoxia ,16 hour hypoxia and 16 hour hypoxia 4 hour reoxygenation conditions respectively. Expressions of HIF 1? and VEGF genes were assessed by the reverse transcription polymerase chain reaction (RT PCR) technique. Results The mRNA expression of HIF 1? gene was kept constant in the different culture conditions,whereas the mRNA expression of VEGF gene increased significantly after 8 or 16 hour hypoxia and decreased after reoxygenation for 4 hours. Conclusions Hypoxia is able to induce the mRNA expression of VEGF gene in the CNE cell, but is unable to do so in HIF 1? mRNA expression. These findings suggest that VEGF upregulation induced by hypoxia be independent HIF 1a transcription.
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Objective To investigate whether chromosome induced aberrations scored with fluorescence in situ hybridization (FISH) predict the radiosensitivity of human tumor cell lines. Methods Three human cell lines with different radiosensitivities(nasopharyngeal cell line CNE, lung adenocarcinoma cell line SPC, and breast adenocarcinoma cell line MCF 7) were used for clonogenic assay. Cells were irradiated with a dose of 1~8?Gy. Radiation induced aberration in a single chromosome (number 8) was measured at 24?h after irradiation of 2, 4 and 6?Gy.Results Radiation induced aberration in chromosome 8 reflected the radiosensitivity in CNE, SPC and MCF 7 cells 24 h after irradiation. It was associated with survival fraction at 2?Gy (r=0.96). Conclusion These results suggest that the radiation induced chromosome aberrations in interphase measured by FISH be a considerable promise for prediction of radiosensitivity in tumor cells.