Objective:To explore the dosimetric characteristics of proton and photon radiotherapy in the treatment of breast cancer.Methods:Four female breast cancer patients who needed radiotherapy at Shandong Cancer Hospital and Institute from January 2024 to May 2024 were selected as the research subjects. The target area ranges of 4 patients were left-sided breast cancer with lymph node involvement, left-sided breast cancer with lymph node involvement and internal mammary node, right-sided breast cancer with lymph node involvement and internal mammary node and synchronous bilateral breast cancer. Intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) plans were designed respectively based on the prescribed dose in the target area and the limits of organs at risk (tomotherapy plan for bilateral breasts). The conformity index (CI), homogeneity index (HI), gradient index (GI) and organs at risk doses were evaluated. The dosimetric characteristics of IMPT and photon radiotherapy were compared.Results:Both IMPT and photon radiotherapy plans of the 4 breast cancer cases met the clinical dose requirements. The HI value of IMPT plans (0.10-0.14) was comparable to that of photon radiotherapy plans (0.10-0.12), and the average CI of the photon radiotherapy plans was 0.10 higher than that of the IMPT plans, and the average GI was 0.55 lower than that of the IMPT plans. The D mean of ipsilateral lung and heart of IMPT was lower, especially in the low-dose area (V 0-3), which was significantly lower than the photon radiotherapy plans, D mean of ipsilateral lung was reduced by 12.2%, 6.1%, 16.1% and 34.8%, respectively, D mean of heart was reduced by 47.2%, 57.0%, 72.4% and 83.0%, respectively. The ipsilateral lung V 20 of IMPT was not lower than photon radiotherapy plans (unilateral breast: IMPT was 30.0%-34.0%, IMRT was 29.0%-35.9%) . Conclusions:IMPT significantly reduces the D mean to the ipsilateral lung and heart while ensuring dose coverage of the target in breast cancer, preventing more volume of surrounding normal tissues from being irradiated. However, IMPT does not show much more advantage than photon radiotherapy plans in the ipsilateral lung V 20.

Objective:To explore the optimal duration of preoperative imatinib therapy in patients with locally advanced gastrointestinal stromal tumors (GIST) in order to optimize surgical timing and long-term survival benefits.Methods:A total of 171 patients with locally advanced GIST who received preoperative imatinib therapy and subsequent surgical resection between November 2012 and October 2024 at Fujian Cancer Hospital and Union Hospital of Fujian Medical University were retrospectively analyzed. Patients were divided into three groups according to the duration of preoperative imatinib treatment: short-term (≤6 months, n=50), intermediate-term (7-12 months, n=87), and long-term (>12 months, n=34). Imaging response, pathological efficacy, recurrence-free survival (RFS), and overall survival (OS) were compared among the groups. Univariate and multivariate Cox regression analyses were used to identify the optimal treatment duration. Results:The median duration of preoperative imatinib therapy was 9 (6, 12) months. After treatment, the average maximum tumor diameter decreased from (10.37±5.74) cm to (6.99±4.34) cm, with an average shrinkage of 31.5%. The objective response rates in the short-, intermediate-, and long-term groups were 50.0% (25/50), 58.6% (51/87), and 52.9% (18/34), respectively; high-grade pathological response rates were 28.0% (14/50), 37.9% (33/87), and 29.4% (10/34), with no statistically significant differences among groups (all P>0.05). With a median follow-up of 46 months, 39 patients experienced recurrence and 20 died. The intermediate-term group had 3- and 5-year RFS rates of 87.1% and 79.6%, respectively, significantly better than those of the short-term group (75.5% and 55.5%, P=0.004). The long-term group had 3- and 5-year RFS rates of 85.3% and 75.5%, which were between the other two groups, but not significantly different (all P>0.05). For OS, the intermediate-term group had 3- and 5-year rates of 97.3% and 92.7%, superior to the short-term group (84.4% and 72.4%, P=0.007), while the long-term group (88.2% and 79.4%) showed no significant advantage (all P>0.05). Stratified analysis revealed that among non-gastric primary tumor patients with c-Kit exon 11 mutations, partial response on imaging, or postoperative imatinib ≤24 months, the intermediate-term group had significantly better RFS and OS than the short-term group (all P<0.05), but had no differences compared to the long-term group ( P>0.05). Multivariate Cox regression analysis indicated that preoperative imatinib duration was not an independent factor for RFS ( P>0.05), but treatment for 7-12 months was an independent protective factor for OS ( HR=0.275, 95% CI: 0.089-0.851, P=0.025), while prolonging therapy beyond 12 months conferred no additional OS benefit ( P>0.05). Conclusions:In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

Objective:To explore the optimal duration of preoperative imatinib therapy in patients with locally advanced gastrointestinal stromal tumors (GIST) in order to optimize surgical timing and long-term survival benefits.Methods:A total of 171 patients with locally advanced GIST who received preoperative imatinib therapy and subsequent surgical resection between November 2012 and October 2024 at Fujian Cancer Hospital and Union Hospital of Fujian Medical University were retrospectively analyzed. Patients were divided into three groups according to the duration of preoperative imatinib treatment: short-term (≤6 months, n=50), intermediate-term (7-12 months, n=87), and long-term (>12 months, n=34). Imaging response, pathological efficacy, recurrence-free survival (RFS), and overall survival (OS) were compared among the groups. Univariate and multivariate Cox regression analyses were used to identify the optimal treatment duration. Results:The median duration of preoperative imatinib therapy was 9 (6, 12) months. After treatment, the average maximum tumor diameter decreased from (10.37±5.74) cm to (6.99±4.34) cm, with an average shrinkage of 31.5%. The objective response rates in the short-, intermediate-, and long-term groups were 50.0% (25/50), 58.6% (51/87), and 52.9% (18/34), respectively; high-grade pathological response rates were 28.0% (14/50), 37.9% (33/87), and 29.4% (10/34), with no statistically significant differences among groups (all P>0.05). With a median follow-up of 46 months, 39 patients experienced recurrence and 20 died. The intermediate-term group had 3- and 5-year RFS rates of 87.1% and 79.6%, respectively, significantly better than those of the short-term group (75.5% and 55.5%, P=0.004). The long-term group had 3- and 5-year RFS rates of 85.3% and 75.5%, which were between the other two groups, but not significantly different (all P>0.05). For OS, the intermediate-term group had 3- and 5-year rates of 97.3% and 92.7%, superior to the short-term group (84.4% and 72.4%, P=0.007), while the long-term group (88.2% and 79.4%) showed no significant advantage (all P>0.05). Stratified analysis revealed that among non-gastric primary tumor patients with c-Kit exon 11 mutations, partial response on imaging, or postoperative imatinib ≤24 months, the intermediate-term group had significantly better RFS and OS than the short-term group (all P<0.05), but had no differences compared to the long-term group ( P>0.05). Multivariate Cox regression analysis indicated that preoperative imatinib duration was not an independent factor for RFS ( P>0.05), but treatment for 7-12 months was an independent protective factor for OS ( HR=0.275, 95% CI: 0.089-0.851, P=0.025), while prolonging therapy beyond 12 months conferred no additional OS benefit ( P>0.05). Conclusions:In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

One of the distinct hallmarks of cancer cells is aerobic glycolysis (Warburg effect). Lactate dehydrogenase A (LDHA) is thought to play a key role in aerobic glycolysis and has been extensively studied, while lactate dehydrogenase C (LDHC), an isoform of LDHA, has received much less attention. Here we showed that human LDHC was significantly expressed in lung cancer tissues, overexpression of Ldhc in mice could promote tumor growth, and knock-down of LDHC could inhibit the proliferation of lung cancer A549 cells. We solved the first crystal structure of human LDHC4 and found that the active-site loop of LDHC4 adopted a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Moreover, we found that (ethylamino) (oxo)acetic acid shows about 10 times selective inhibition against LDHC4 over LDHA4 and LDHB4. Our studies suggest that LDHC4 is a potential target for anticancer drug discovery and (ethylamino) (oxo)acetic acid provides a good start to develop lead compounds for selective drugs targeting LDHC4.

Objective To evaluate the role of hippocampal CD200 receptor 1(CD200R1)in peri-operative neurocognitive disorders(PND)in mice.Methods Sixty clean-grade male C57BL/6 mice,aged 9-10 months,weighing 32-38 g,were used in the study.The experiment was performed in two parts.Ex-periment Ⅰ Thirty-six mice were divided into 2 groups(n＝18 each)using a random number table meth-od: control group(group C)and PND group.Group C only received isoflurane anesthesia.Partial left lo-bectomy of the liver was performed under isoflurane anesthesia in group PND.Contextual fear conditioning test was performed at 1,3 and 7 days after surgery,and the freezing time was recorded.The mice were then sacrificed,and the hippocampus was isolated for determination of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)contents(by enzyme-linked immunosorbent assay)and CD200 and CD200R1 expression(by Western blot).ExperimentⅡ Twenty-four mice were divided into 2 groups(n＝12 each)using a random number table method: CD200-Fc group and IgG1-Fc group.Recombinant proteins CD200-Fc and human IgG1-Fc were injected into the lateral cerebral ventricle in CD200-Fc group and IgG1-Fc group,respectively.Partial left lobectomy of the liver was performed after the end of injection.Contextual fear conditioning test was performed at 1 and 3 days after surgery,and the freezing time was recorded.Re-sults Experiment Ⅰ Compared with group C,the freezing time in the contextual fear conditioning test was significantly shortened,and the contents of IL-1β were increased at 1 and 3 days after surgery,the contents of TNF-α were increased at 3 and 7 days after surgery,and the expression of CD200 and CD200R1 was up-regulated at 1 day after surgery in group PND(P＜0.05).ExperimentⅡ Compared with IgG1-Fc group,the freezing time in the contextual fear conditioning test was significantly prolonged at 1 day after surgery in CD200-Fc group(P＜0.05).Conclusion Up-regulated expression of hippocampal CD200R1 is the endogenous protective mechanism of PND in mice.

Objective: To evaluate the role of hippocampal CD200 receptor 1 (CD200R1) in perioperative neurocognitive disorders (PND) in mice. Methods: Sixty clean-grade male C57BL/6 mice, aged 9-10 months, weighing 32-38 g, were used in the study.The experiment was performed in two parts.Experiment Ⅰ Thirty-six mice were divided into 2 groups (n=18 each) using a random number table method: control group (group C) and PND group.Group C only received isoflurane anesthesia.Partial left lobectomy of the liver was performed under isoflurane anesthesia in group PND.Contextual fear conditioning test was performed at 1, 3 and 7 days after surgery, and the freezing time was recorded.The mice were then sacrificed, and the hippocampus was isolated for determination of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) contents (by enzyme-linked immunosorbent assay) and CD200 and CD200R1 expression (by Western blot). Experiment Ⅱ Twenty-four mice were divided into 2 groups (n=12 each) using a random number table method: CD200-Fc group and IgG1-Fc group.Recombinant proteins CD200-Fc and human IgG1-Fc were injected into the lateral cerebral ventricle in CD200-Fc group and IgG1-Fc group, respectively.Partial left lobectomy of the liver was performed after the end of injection.Contextual fear conditioning test was performed at 1 and 3 days after surgery, and the freezing time was recorded. Results: Experiment Ⅰ Compared with group C, the freezing time in the contextual fear conditioning test was significantly shortened, and the contents of IL-1β were increased at 1 and 3 days after surgery, the contents of TNF-α were increased at 3 and 7 days after surgery, and the expression of CD200 and CD200R1 was up-regulated at 1 day after surgery in group PND (P<0.05). Experiment Ⅱ Compared with IgG1-Fc group, the freezing time in the contextual fear conditioning test was significantly prolonged at 1 day after surgery in CD200-Fc group (P<0.05). Conclusion Up-regulated expression of hippocampal CD200R1 is the endogenous protective mechanism of PND in mice.

ObjectiveTo study the feasibility of RapidArc (RA) associated with active breath coordinator (ABC)for hepatocelluar carcinoma (HCC)radiotherapy comparing of three-dimensional conformal radiotherapy (3DCRT),intensity modulated radiotherapy (IMRT),RA treatment plans in different breath status.Methods12 HCC cases were selected.Three series CT scanning were completed in Free Breathing (FB),End Inspiration Hold (EIH) and End Expiration Hold (EEH) associated with ABC device.3DCRT,IMRT and RA (three 135° arcs) treatment plans were respectively designed on planning target volume (PTV) in different breath status.The dosimetric differences among 3 DCRT,IMRT and RA,among RA plans under different breath status were compared.ResultsThe PTV in FB was larger than in EEHand EIH (160.8 cm3,89.5 cm3,83.1 cm3,F=6.63,P=0.004). The conformity index and homogeneity index of RA plans were better than IMRT and 3DCRT ( 0.92,0.90,0.77,F =72.55,P =0.000 ;0.90,0.89,0.84,F =125.49,P =0.000 ) ;the V20,V30,V40 of normal liver in 3DCRT were higher than IMRT and RA (24％,20％,19％,F=3.56,P =0.032;13％,10％,10％,F=5.74,P =0.004;8％,5％,6％,F =3.72,P =0.027).The normal liver mean dose,V10,V20,V30,V40 of RA plans in FB were higher than in EEH and EIH ( 13.46 Gy,10.25 Gy,9.48 Gy,F =3.627,P =0.038 ;46％,35％,32％,F =2.96,P=0.066;24％,16％,16％,F=3.69,P=0.036;13％,8％,8％,F=4.28,P=0.022;8％,5％,5％,F =2.39,P =0.108 ).The duodenum D5 cm3 of RA in EEH was lower than in FB and EIH (8.78 Gy,19.35 Gy and 11.67 Gy,F =1.56,P =0.224 ).The mean monitor units for 3 DCRT,IMRT,RA was 254.06 MU,626.33 MU and 550.28 MU ( F =147.35,P =0.000 ),while the mean treatment time was 135 s,540 s and 130 s respectively (F =62.83,P =0.000).ConclusionsThe RapidArc applying three 135°arcs with ABC in HCC radiotherapy can achieve better PTV coverage than IMRT with fewer monitor units,shorter treatment time and sparing more normal liver.

Objective To evaluate the accumulated doses to normal tissues and organs at risks (OARs) of patients with lung cancer in radiotherapy plans by using the deformable registration method,and make comparison with the empirical calculation method.Methods Ten patients with lung cancer were analyzed retrospectively.3D-CRT or IMRT plans were designed before treatment. CT to simulator was rescanned and the same treatment plan was redesigned during radiotherapy. Based on the deformable registration method,the Mimvista software was used to calculate the accumulated doses to normal tissues and OARs in two CT images respectively.The empirical estimation algorithm was calculated by the linear relationship between the fractions and the total prescribed dose.Results The target coverage of patients had no significant difference in two plans.There were no significant differences in all the dose volume parameters for normal tissues and OARs,except the mean dose to right lung( t =2.98,P ＜ 0.05 ) when the the same plan was conducted in position-setting and reposition CT images.Conclusions The empirical estimation for the accumulated dose could be used to evaluate the dose and volume parameters for normal tissues and OARs in lung cancer by the same plan.

Purpose To investigate the dosimetric differences among RapidArc (RA) plans which were designed on different target volumes in hepatocellular carcinoma (HCC).Methods A total of 10 HCC patients underwent 3D-CT scan under free breathing ( FB),end inspiration hold ( EIH ) associated with active breath coordinator (ABC) and 4D-CT scan.The 4D-CT were sorted into 10 sets of CT images according to respiratory cycle.The gross tumor volume (GTV) was manually contoured on different CT images.The individual internal gross target volume ( IGTV1 ) was obtained from 4D-CT,and the individual margins from GTVFB to IGTV1.IGTV2 were obtained from GTVFB using individual margins.The planned target volumes (PTV-1,PTV-2,PTV-3 and PTV-4 ) were obtained from GTVFB,IGTV1,IGTV2 and GTVEIA applying different margins.The RA plans (RA1,RA2,RA3 and RA4 ) were designed from different PTVs,and for RA1,RA2 and RA3 the simple 358° arc were used,while three 135° arcs were used for RA4.The dosimetric differences were compared.Results The PTV-1 and PTV-3 were larger than PTV-2 and PTV-4; the mean values of PtV-1/PTV-2 and PTV-1/PTV-4 were 2.5 and 1.9,respectively.There were no significant differences in conformal index,homogeneity index,maximum dose,and minimum dose of PTV among 4 RA plans.The irradiation dose of normal liver of RA3 and RA4 were 8.23 Gy and 7.63 Gy respectively,both significantly lower than those of RA1 and RA2 (10.21 Gy,9.62 Gy,x2 =10.68,P ＜0.05 ),and the V30of RA3 and RA4 were 5.24％ and 5.05％ respectively,both significantly lower than those of RA1 and RA2 (7.76％,6.12％,x2 =14.76,P ＜ 0.05 ).There were no significant differences in irradiation doses of stomach and duodenum among different plans.Conclusions Using 4D-CT or ABC technology with RapidArc in HCC can define the target volume accurately and achieve prefect dose distribution sparing more normal liver volume,compared to the traditional margins.4D-CT and ABC play similar roles in sparing normal liver.

Objective To compare and analyze the dosimetric characteristics of the intensity-modulated arc therapy (RapidArc) combined with active breathing coordinator (ABC) in the thoracic esophageal carcinoma radiation therapy. Methods Ten thoracic esophageal carcinoma patients undergoing radiotherapy were selected for this study.The CT simulations were performed under three breath patterns respectively:moderate deep inspiration breath-hold (mDIBH) with ABC aid; Set the trigger threshold to 80％ of the peak of the respiration curve; and free breathing (FB).Based on the corresponding CT image sets,three treatment plans were generated for each patient respectively:Arc-ABC( three small arcs),ArcFB (consisted of two coplanar full arcs) and IMRT-FB plan.The following dosimetric parameters were compared among different plans:D2％,D98％,V95,homogeneity index ( HI),conformal index ( CI ) the percentage of volume receiving dose of over x Gy (Vx),monitor unit (MU),control points and treatment time.Results The planning target volume ( PTV ) of FB was 376 cm3 which decreased to 260 cm3 after using ABC.For mDIBH and FB patients,the total lung volumes were 5964.6 cm3(35％ more than FB) and 3838.8 cm3 respectively; the heart volumes were 524.4 cm3 and 642.7 cm3 respectively. No significant difference was observed among Arc-ABC,IMRT-FB and Arc-FB in terms of D2,D98,V95,CI and HI.For Arc-ABC plans,there were significant decreases of radiation dose in total-lung's V10,V20,V30,V40 and mean lung dose ( F =4.38,5.34,4.07,3.89,4.28,P ＜0.05).Various dose decreases of heart V20,V3,V40,Dmean and spinal cord Dmax were observed,yet no statistically significant difference existed.The MUs and total control points of Arc-ABC plans were significantly lower than other plans ( F =26.86,12.56,P ＜ 0.05 ).Conclusions When thoracic esophageal carcinoma patients were treated with radiotherapy,the combined utilization of RapidArc and ABC can potentially decrease the volume of irradiated lung yet escalate the dose in target.