Comparison of the displacements of peripheral lung cancer based on 4D CT scan and 3D CT scan assisted with active breathing control / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the position, displacement, degree of inclusion (DI) and matching index (MI) of the gross tumor volume (GTV) for peripheral lung cancer based on 4-dimensional CT (4D CT) and 3-dimensional CT (3D CT) assisted with active breathing control (ABC).</p><p><b>METHODS</b>Eighteen patients with peripheral lung cancer underwent 4D CT simulation scan during free breathing and 3D CT simulation scans in end-inspiratory hold (CTEIH) and end-expiratory hold (CTEEH) in turn. The 4D CT images from each respiratory cycle were sorted into 10 phases. phase 0 was defined as end-inspiratory phase (CT0), and phase 50 was defined as end-expiratory phase (CT50). The GTVs were delineated separately on CT0, CT50, CTEIH and CTEEH images, and then GTV0, GTV50, GTVEIH and GTVEEH were constructed, respectively.</p><p><b>RESULTS</b>The median distances between the centroids of GTV0 and GTVEIH, GTV50 and GTVEEH were 3.9 mm and 3.4 mm in all patients, 3.2 mm and 3.1 mm in the upper lobe group, and 5.0 mm and 4.7 mm in the lower lobe group, respectively. In the upper lobe group, the GTV0 and GTVEIH were 65.9% and 63.1%, and the median mutual DIs of GTV50 and GTVEEH were 67.5%, 63.1%, respectively. In the lower lobe group, the GTV0 and GTVEIH were 35.3% and 21.4%, and the median mutual DIs of GTV50 and GTVEEH were 27.8% and 24.8%, respectively. In the upper lobe group, the median MI of GTV0 and GTVEIH was 0.5, and the median MI of GTV50 and GTVEEH was 0.6. In the lower lobe group, the median MI of GTV0 and GTVEIH was 0.2, and the median MI of GTV50 and GTVEEH was 0.3. Whether in the upper or lower lobe groups, all the differences between displacements of centroid positions of GTVEIH and GTVEEH (ABC displacement) and GTV0 and GTV50 (4D displacement ) were <1 mm in three dimensional directions (all P>0.05).</p><p><b>CONCLUSIONS</b>The target displacement of tumors based on 3D CT scanning in end-inspiratory hold and end-expiration hold can be used to construct internal target volume instead of that based on 4D CT scanning in extreme phase for peripheral lung cancers, but spatital mismatches of GTVs are obvious between extreme phases in 4D CT and corresponding phases in 3D CT assisted with ABC, especially for tumors of smaller volume and with larger motion amplitude.</p>

Comparison of three methods to delineate internal gross target volume of the primary hepatocarcinoma based on four-dimensional CT simulation images / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the position and magnitude of internal target gross volume (IGTV) of primary hepatocarcinoma delineated by three methods based on four-dimensional computed tomography (4D-CT) and to investigate the relevant factors affecting the position and magnitude.</p><p><b>METHODS</b>Twenty patients with primary hepatocarcinoma after transcatheter arterial chemoembolization (TACE) underwent big bore 4D-CT simulation scan of the thorax and abdomen using a real-time position management (RPM) system for simultaneous record of the respiratory signals. The CT images with respiratory signal data were reconstructed and sorted into 10 phase groups in a respiratory cycle, with 0% phase corresponding to end-inhale and 50% corresponding to end-exhale. The maximum intensity projection (MIP) image was generated. IGTVs of the tumor were delineated using the following three methods: (1) The gross tumor volume (GTV) on each of the ten respiratory phases of the 4D-CT image set was delineated and fused ten GTV to produce IGTV10; (2) The GTVs delineated separately based on 0% and 50% phase were fused to produce IGTV(IN+EX); (3) The visible tumor on the MIP image was delineated to produce IGTV(MIP). Twenty patients were divided into groups A and B based on the location of the target center,and were divided into groups C and D based on the tumor maximum diameter. The patients were divided into groups E and F based on the three-dimensional (3D) motion vector of the target center. The position of the target center, the volume of target, the degree of inclusion (DI) and the matching index (MI) were compared reciprocally between IGTV10, IGTV(IN+EX) and IGTV(MIP), and the influence of the tumor position and 3D motion vector on the related parameters were compared based on the grouping.</p><p><b>RESULTS</b>The average differences between the position of the center of IGTVs on direction of X, Y and Z axes were less than 1.5 mm, and the difference was statistically not significant. The volume of IGTV10 was larger than that of IGTV(IN+EX), but the difference was not significant (t = 0.354, P = 0.725). The volume of IGTV10 was larger than that of IGTV(MIP) but the difference was not significant (t = -0.392, P = 0.697). The ratio of IGTV(IN+EX) to IGTV10 was 0.75 +/- 0.15 and the ratio of IGTV(MIP) to IGTV10 was 0.78 +/- 0.14. The DI of IGTV(IN+EX) in IGTV10 was (74.85 +/- 15.09)% and that of IGTV(MIP) in IGTV10 was (68.87 +/- 13.69)%. The MI between IGTV10 and IGTV(IN+EX), IGTV10 and IGTV(MIP) were 0.75 +/- 0.15 and 0.67 +/- 0.13, respectively. The median of ratio of IGTV(IN+EX)/ IGTV10 was 0.57 in group A versus 0.87 in group B, statistically with a significant difference between the groups A and B (Z = -3.300,P = 0.001). The median of ratio of IGTV(MIP)/IGTV10 was 0.51 in the group A and 0.72 in group B, with a significant difference between the groups A and B (Z = -3.413, P = 0.001). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.79 in group C versus 0.74 in group D, with a difference not significant (Z = -0.920, P = 0.358). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in group C versus 0.80 in group D, with a non-significant difference (Z = -0.568, P = 0.570). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.87 in group E versus 0.68 in group F, with a significant difference between the two groups (Z = -2.897, P = 0.004). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in the group E versus 0.81 in the group F, with a non-significant difference (Z = -0.568, P = 0.570).</p><p><b>CONCLUSIONS</b>The center displacement of the IGTVs delineated separately by the three techniques based on 4D-CT images is not obvious. IGTV(IN+EX) and IGTV(MIP) can not replace IGTV10, however, IGTV(IN+EX) is more close to IGTV10 comparing with IGTV(MIP). The ratio of IGTV10 and IGTV(MIP) is correlated to the 3D motion vector of the tumor. When the tumor is situated in the upper part of the liver and with a 3D motion vector less than 9 mm, IGTV10 should be the best IGTV.</p>

Displacement of the silver clips in surgical cavity based on four-dimensional CT images for patients undertaking external-beam partial breast irradiation after breast-conserving surgery / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the displacement of the selected clips and the center of the geometry consisted of all the clips in the surgical cavity measured on the basis of four-dimensional computed tomography (4D-CT) simulation images.</p><p><b>METHODS</b>Fourteen breast cancer patients after breast-conserving surgery were recruited for external beam partial-breast irradiation (EB-PBI), and received large aperture CT simulation. The 4D-CT image data sets were collected when the patient was in the free breathing state. Using the Varian Eclipse treatment planning system, the selected four clips in the cavity were separately delineated on the CT images from 10 phases of the breath cycle, and all of the clips in the cavity were marked to obtain the geometry. Then the displacement of the four selected clips and the center of the geometry in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured. The differences of the displacement were compared.</p><p><b>RESULTS</b>The displacements in the AP and SI directions were always greater than the displacement in LR direction for the same selected clip. The difference of the displacements in the same direction of the different selected clips was not statistically significant (P>0.05). The displacements of the geometry center consisted of all of the clips in the LR, AP, SI directions were (1.34±0.39) mm, (2.01±1.02) mm and (1.89±1.03) mm, respectively, and the difference of the displacements between LR and AP, LR and SI were all statistically significant (P<0.05). In the same directions (LR, AP and SI), the displacement of geometry center was always greater than the displacement of the selected clips, and the difference except SI direction was all statistically significant (P<0.05). In the SI direction, the association between the displacement of geometry center and the upper clip, geometry center and the lower clip was statistically significant (P<0.05).</p><p><b>CONCLUSION</b>When the target for EB-PBI is defined on the basis of 4D-CT simulation images, the displacement of the selected clips at the border of the surgical cavity is not qualified to substitute the displacement of the target defined basing on all of the clips in the surgical cavity.</p>

Measurement of intrafraction displacement of the mediastinal metastatic lymph nodes of non-small cell lung cancer based on four-dimensional computed tomography (4D-CT) / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To measure the intrafraction displacement of the mediastinal metastatic lymph nodes of non-small cell lung cancer (NSCLC) based on four-dimensional computed tomography (4D-CT), and to provide the basis for the internal margin of metastatic mediastinal lymph nodes.</p><p><b>METHODS</b>Twenty-four NSCLC patients with mediastinal metastatic lymph nodes confirmed by contrast enhanced CT (short axis diameter ≥ 1 cm) were included in this study. 4D-CT simulation was carried out during free breathing and 10 image sets were acquired. The mediastinal metastatic lymph nodes and the dome of ipsilateral diaphragma were separately delineated on the CT images of 10 phases of breath cycle, and the lymph nodes were grouped as the upper, middle and lower mediastinal groups depending on the mediastinal station. Then the displacements of the lymph nodes in the left-right, anterior-posterior, superior-inferior directions and the 3-dimensional vector were measured. The differences of displacement in three directions for the same group of metastatic lymph nodes and in the same direction for different groups of metastatic lymph nodes were compared. The correlation between the displacement of ipsilateral diaphragma and mediastinal lymph nodes was analyzed in superior-inferior direction.</p><p><b>RESULTS</b>The displacements in left-right, anterior-posterior and superior-inferior directions were (2.24 ± 1.55) mm, (1.87 ± 0.92) mm and (3.28 ± 2.59) mm for the total (53) mediastinal lymph nodes, respectively. The vectors were (4.70 ± 2.66) mm, (3.87 ± 2.45) mm, (4.97 ± 2.75) mm and (5.23 ± 2.67) mm for the total, upper, middle and lower mediastinal lymph nodes, respectively. For the upper mediastinal lymph nodes, the displacements in left-right, anterior-posterior and superior-inferior directions showed no significant difference between each other (P > 0.05). For the middle mediastinal lymph nodes, the displacements merely in anterior-posterior and superior-inferior directions showed significant difference (P = 0.005), while the displacements were not significantly different in the left-right and anterior-posterior, left-right and superior-inferior directions (P > 0.05). The displacements of the total and the lower mediastinal lymph nodes in left-right and superior-inferior, or anterior-posterior and superior-inferior directions were significantly different (P < 0.05), but was not significantly different in left-right and anterior-posterior directions (P > 0.05). The displacements of different group of mediastinal lymph nodes in a single direction or vector showed no significant difference (P > 0.05). In the superior-inferior direction, the correlation between the displacements of ipsilateral diaphragma and mediastinal lymph nodes were not statistically significant (P > 0.05).</p><p><b>CONCLUSIONS</b>During free breathing, the differences between the intrafractional displacement of mediastinal metastatic lymph nodes in the same direction and its station were not statistically significant. The displacements of the total mediastinal metastatic lymph nodes in the superior-inferior direction were greater than that in the left-right and anterior-posterior directions, especially for the middle and lower mediastinal metastatic lymph nodes. There was no significant correlation between the displacements of ipsilateral diaphragma and the mediastinal metastatic lymph nodes in the superior-inferior direction, so it was unreasonable to estimate and predict the displacement of mediastinal metastatic lymph nodes by the displacement of ipsilateral diaphragma.</p>

Immunogenicity and safety of DTaP-IPV//PRP-T combined vaccine in infants in China / 中华流行病学杂志

Objective The aim of this study was to demonstrate the immunogenicity and safety of diphtheria, tetanus, pertussis (acellular, component) , poliomyelitis (inactivated) vaccine (adsorbed) and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV//PRP-T) combined vaccine compared with commercially available DTaP (diphtheria, tetanus and pertussis), Haemophilus influenzae type b (Hib), tetanus conjugate and IPV monovalent vaccine. Methods Subjects were randomly divided into three groups, Group A and Group B were DTaP-IPV//PRP-T combined vaccine (PENTAXIMTM) vaccinated at 2,3,4 months of age or 3,4, 5 months of age respectively; Group C was commercially available DTaP. Hib tetanus conjugate (Act-HIBTM) and IPV (IMOVAX PolioTM) vaccines vaccinated at 3,4, 5 months of age. All groups received booster dose at 18 to 20 months of age, with antibody titers tested. Non-inferiority analysis was demonstrated in terms of seroprotection / seroconversion rates between Group A, Group B respectively and Group C. Safety information was collected after each vaccination to assess the safety of investigational vaccines. Results The non-inferiority of DTaP-IPV//PRP-T combined vaccine vaccinated at 2,3,4 or 3,4, 5 months of age versus DTaP, Hib tetanus conjugate and IPV vaccine was demonstrated for all vaccine antigens in both primary and booster phases in terms of seroprotection/seroconversion rates. DTaP-IPV//PRP-T combined vaccine was well tolerated. The rate of solicited/unsoliciated severe adverse reactions was very low and similar to the control vaccines. Conclusion DTaP-IPV//PRP-T combined vaccine was highly immunogenic with good safety profile in Chinese infants, which was comparable to the commercially available control vaccines.

Dynamic change of mother-source neutralizing antibodies against enterovirus 71 and coxsackievirus A16 in infants / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) are major causative agents for hand, foot and mouth disease (HFMD). Studies indicate that the frequent HFMD outbreaks result in a few hundreds children's death in China in recent years. The vaccine and other research for HFMD need to be developed urgently.</p><p><b>THE AIMS OF OUR STUDY WERE</b>to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course.</p><p><b>METHODS</b>Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively.</p><p><b>RESULTS</b>Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% (106/133) and 92.5% (123/133), respectively; geometric mean titers (GMTs) were 29.0 and 61.9; 75.9% (101/133) prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% (34/133) and 38.3% (51/133) in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months (82.6) compared with that at two months (P < 0.05), showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring (0.75%) at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months.</p><p><b>CONCLUSIONS</b>The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.</p>

Genetic characterization of enterovirus 71 complete genome isolated in Beijing, 2008 / 中华流行病学杂志

Objective To investigate the characterization of the complete genome of EV71 in Beijing, 2008 and to provide basis for selecting appropriate virus strain to develop vaccine. Methods 12 throat swab samples were collected from children with hand-foot-mouth disease (HFMD). One sample named 08YM-3 was cultured and isolated in vero cells. Viral RNA was extracted and carried out by RT-PCR and 5' , 3' rapid amplification of eDNA ends (RACE) to obtain the sequence from 08YM-3. PCR products were cloned and analyzed. Nucleotide identity between sequences was calculated and sequence alignments were made to generate phylogenetic trees using MegAlign in DNAStar. Results 3 clones were constructed that covered EV71 complete genome. Data from sequences analysis showed that this viral strain named BJ08 shared 95.6%-96.7%, 88.3%-96.1%,78.1%-94.0%,90.8%-94.6%, 85.9%-94.1% and 90.9%-93.9% in 5' UTR, PI, P2, P3, 3' UTR region and complete genome with C4 subtype, respectively. B J08 showed low nucleotides identity (<90%) with other subtypes. Phylogenetic trees established from alignment of the complete genome and VPI region indicated that B J08 belonged to C4 subtype. BJ08 and C4 subtype strains shared the same amino acids in 6 sites in VP1 region, which were associated with EV71 subtype. There was no mutation in VP1 antigen epitope (92-107aa). Conclusion This BJ08 strain belonged to C4 subtype. Further study on EV71 complete genome would have great significance for vaccine research.

Study on the safety and immunogenicity of group A + C meningococcal polysaccharide vaccine / 中华流行病学杂志

<p><b>OBJECTIVE</b>In order to evaluate the safety and immunogenicity of group A + C meningococcal polysaccharide vaccine, a controlled field trial was performed among children at 6-24 months and 5-13 years old in Longsheng county, Guangxi Zhuang Autonomous Region.</p><p><b>METHODS</b>More than 600 children were selected in this trial. 428 children, aged 6-24 month-old and 5-13 year-old were involved in two experimental groups and were inoculated 100 microg of group A + C meningococcal polysaccharide vaccine. 103 children in positive control group were inoculated 50 microg of group A meningococcal polysaccharide vaccine while 94 children in negative control group were inoculated 30 microg of Typhoid Vi polysaccharide vaccine. Both systemic and local reactions were observed in each group at 6 h,24 h,48 h and 72 h after inoculation. Blood samples were collected in all children before and at 1 month after inoculation. Additionally, at least 50 blood samples were taken in each experimental group at 6 and 12 months after inoculation. Serum bactericidal antibody was tested by micro bactericidal test.</p><p><b>RESULTS</b>Both systemic and local reactions were mild in two experimental groups with only 3 children (0.7%) had > or = 37. 6 degrees C fever, 4 children (0.9%) appeared mild areola but all adverse reaction disappeared within 48 hours. In 5-13 year-old experimental group, the rates for four-fold increase of bactericidal antibody were 96.59% and 92.15% to group A and group C meningococcus respectively at 1 month after inoculation, and remained 90.91% and 90.08% at 12 months after inoculation.</p><p><b>CONCLUSION</b>Group A + C meningococal polysaccharide vaccine was safe and having good immunogenicity among Chinese children.</p>