Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

Objective:To explore the amplitude of normal kidney motion in the 3D direction and its influencing factors under free-breathing condition.Methods:Clinical data of 28 patients with a KPS score≥80 who received 4D CT scan from March 2018 to March 2019 were collected. All patients were diagnosed with liver, pancreatic or lung tumors. The kidney was outlined and the geometric center and 3D coordinate values were recorded. The motion of bilateral kidneys in each direction and the 3D direction was calculated. The volume of kidney and surrounding organs, age, sex, height and body mass index (BMI) were recorded. Clinical data were statistically compared by t-test or nonparametric test. Results:The motion of the left and right kidneys in the the sup-inf (SI) direction were the largest up to (8.39±3.18) mm and (7.71±3.55) mm. The motion amplitudes of bilateral kidneys in male patients were significantly larger than those of the female counterparts in the left-right (LR), SI and 3D directions (all P<0.05). The motion amplitudes of bilateral kidneys in patients taller than 165 cm were significantly larger than those of their counterparts with a height of ≤165 cm (all P<0.05). Patients with a BMI≥25 kg/m 2 had significantly larger motion amplitudes of the left kidney in the LR and ant-post (AP) directions compared with those of normal weight counterparts (all P<0.05). The motion amplitude of the left kidney in the AP direction in patients with the left kidney volume of >180 cm 3 was significantly larger than that of patients with smaller left kidney volume ( P=0.014). Age was not significantly associated with kidney motion in each direction ( P>0.05). Conclusions:Kidney motion mainly occurs in the SI direction. The kidney motion amplitudes in male and taller patients are larger. Special attention should be paid to the use of breath motion control device to decrease the normal tissue damage.

Objectives:To investigate the efficacy and toxicity of the full coverage radiation to primary and all metastatic lesions in patients with oligometastatic castration-resistant prostate cancer (CRPC).Methods:Forty-four patients with oligometastatic CRPC was retrospective analyzed from Oct. 2011 to Jun. 2017 at Peking University 1 st Hospital. Before radiotherapy, average age was 72(57-86), the median value of initial PSA was 38.545 (6.640-1 066.000)ng/ml, the median value of PSA nadir after initial androgen deprivation therapy(ADT) was 0.259(0.011-18.762)ng/ml, the time interval between initial ADT to diagnosis of metastatic castration resistant prostate cancer(mCRPC) was 12(4-96) months, and the median PSA value pre-radiotherapy was 3.765(2.040-187.000) ng/ml. There were 23(52.3%)patients with Gleason score 9-10 and 15(34.0%) patients with Gleason score 8. At the time of initial diagnosis, there was 41(93.2%) cases with stage T 3-T 4, 23(52.3%)cases with lymph node metastasis, and 29 (63.9%) case with distant metastasis. The number of metastatic foci before radiotherapy was 1 in 22(50.0%)cases, 2 in 12(27.3%)cases, 3 in 6(13.6%)cases and 4 in 4(9.1%)cases. There were 3 cases of pelvic lymph node metastasis (6.8%), 9 cases of retroperitoneal lymph node metastasis(20.5%), 21 cases of bone metastasis(47.7%), 11 cases of bone metastasis+ lymph node metastasis(25.0%), and no visceral metastasis. Image-guided volumetric modulated arc therapy(IGRT-VMAT) was used to fully cover primary and metastatic foci. The prostate and seminal vesicle were routinely underwent 76Gy/38 fractions, and the bioequivalent dose(BED 3) was 126.67 Gy. For those with pelvic lymph node metastasis, the drainage area of pelvic lymph node was 46Gy/23 fractions. According to the tolerance of different normal tissues around the lesions, the median BED 3 of local radiotherapy dose in the metastatic foci was 112.26(91.14-140.77)Gy. The efficacy and side effects of all these patients were recorded. Kaplan-meier method was used to analyze the overall survival and the new metastasis-free survival. Results:Only 1 patient had grade 3 urinary tract obstruction and underwent indwelling catheter. All the other patients had grade 1-2 toxic and side effects. After a median follow-up of 34.5(9-96) months, the PSA-nadir after radiotherapy was 0.088(0.003-132.000)ng/ml. Forty(90.9%) patients showed a decrease in PSA after radiotherapy, and 34(77.3%) cases. showed a decrease of >80%. The 1, 3, and 5-year overall survival rates were 90.9%, 54.5%, 36.8%, the 1, 3, and 5-year new metastasis free survival rates were 47.7%, 25.0%, 12.9%, respectively.Conclusion:The full coverage radiotherapy to primary and metastatic lesions showed high PSA response rate, the satisfactory survival and tolerable toxicity in oligometastatic CRPC patients.

Objective:To investigate the efficacy and safety of radiotherapy for all metastases in patients with metachronous oligo-metastatic prostate cancer after radical treatment.Methods:From October 2011 to February 2021, 41 patients with prostate cancer with less than 5 metastases after radical treatment were retrospectively analyzed in a single center. The median age at radiotherapy was 68 (57-81) years. Forty patients (98%) received androgen deprivation therapy (ADT). There were 28 patients in the hormone sensitive (HSPC) group and 13 patients in the hormone resistant (CRPC) group. The median initial PSA was 24.4 (7.4-399.0) ng/ml. Tumor stage: T 2 stage 11 patients, T 3 stage 27 patients, T 4 stage 3 patients.30 patients were in N 0 stage and 11 patients in N 1 stage. Gleason score was 7 in 12 patients, 8 in 9 patients, 9 in 18 patients, and 10 in 2 patients.33 patients were treated with surgery, and 8 patients were treated with radiotherapy. The time span from diagnosis to metastasis was 3.1 (0.2-1.8) years. Conventional imaging examination (CT/ MRI/bone scan) before radiotherapy was used in 7 patients, and PSMA PET/CT examination was used in 34 patients.The median PSA before radiotherapy was 1.3(0.1-33.8) ng/ml. There were 62 metastases in 41 patients, including 1 lesion in 28 patients, 2 lesions in 9 patients, 3 lesions in 2 patients, and 5 lesions in 2 patients. Fifty-four patients had bone metastases and eight had retroperitoneal lymph node metastases. Twenty-two bone metastases were located in the pelvis, 18 in the vertebral body, 12 in the ribs, one in the femur and one in the sternum.The median metastatic volume was 5.8(0.2-81.7) cm 3.Daily image-guided rotational intensity modulated radiotherapy was used to cover all metastases.Dose segmentation modes include 37.5Gy/7.5Gy/5F, 60Gy/3Gy/20F, 65-70Gy/2.6-2.8Gy/25F.The median biological effective dose (BED 3) was 120 (67-147) Gy. The primary endpoint was biochemical progression-free survival (BPFS), the secondary endpoints were acute and late toxic side effects, local relapse-free survival (LPFS), and overall survival (OS). Results:The median follow-up time was 21 months (range 5-72 months). All patients completed radiotherapy, and 16 patients had grade 1 to 2 acute toxicity and side effects, and no grade 3 or above acute and late stage side effects. 1-year LPFS was 97.1%.The 1-year and 2-year BPFS were 77.5% and 59.2%, respectively. The median BPFS time was 29 months (range 13.9-44.2 months). Univariate analysis showed that the HSPC group ( P<0.001) and the group with total metastatic volume ≤ 5.8cm 3 ( P=0.010) had higher BPFS. The median BPFS time was 37 months in the retroperitoneal lymph node metastases subgroup and 17 months in the bone metastases subgroup ( P=0.141). In the HSPC group, the median BPFS was 30(22-38) months. After radiotherapy, PSA decreased in all 28 patients, and increased in 6 patients. The median BPFS was 12(4-18) months. In the CRPC group, the median BPFS was 4(0-8) months. PSA decreased in 10 patients (76.9%) after radiotherapy, and PSA decreased in 6 patients. The median BPFS was 5(3-28) months. Three patients’PSA did not decrease after radiotherapy, and they were treated with new endocrine therapy drugs, chemotherapy, immunotherapy and other systemic therapy. Conclusions:For patients with metachronous metastases after radical treatment, full coverage radiotherapy has good safety and high local control rate. HSPC patients and patients with low tumor load could be recommended to receive radiotherapy for all metastatic lesions preferentially, and patients with only retroperitoneal lymph node metastases may have better prognosis after radiotherapy than patients with bone metastases.

Objective:To evaluate the dosimetric properties of intensity-modulated proton therapy (IMPT) plans for simulated treatment planning in patients with ventricular tachycardia (VT) using stereotactic ablative body radiotherapy (SABR), in comparison with the volumetric-modulated arc therapy (VMAT).Methods:A total of 25 gross target volume (GTV) of the apical, anterior, septal, inferior and lateral wall of the left ventricle (LV) were delineated on the CT simulation images of 5 patients with complete data. An additional 5 mm GTV margin was added to the internal target volume (ITV), and an additional 3 mm ITV margin was added to the planning target volume (PTV). VMAT and IMPT plans were designed in each target area. Dose prescription was 25 Gy (RBE) in a single fraction. The dosimetric differences of ITV and organ at risk (OAR) were compared between VMAT and IMPT.Results:The median volume of ITV was 45.40 cm 3(26.72-67.59 cm 3). All plans had adequate target coverage(V 95%Rx≥99%). Compared with the VMAT plans, IMPT reduced the D mean of whole heart, pericardium and non-target cardiac tissues (relative difference) by 44.52%, 44.91% and 60.16%, respectively, which also reduced D 0.03 cm 3 of the left anterior descending artery by 17.58%( P<0.05). After stratified analysis according to the lesion sites, IMPT could still reduce the dose of most OAR. However, the D 0.03 cm 3 of LAD and LCX for the lesions in the anterior wall of LV, the D 0.03 cm 3 of LCX in the inferior wall and D 0.03 cm 3 of LAD in the apical wall did not significantly differ (both P>0.05). Conclusions:Both VMAT and IMPT plans can meet the clinical dosimetric requirements when SABR is simulated in patients with VT. However, IMPT can lower the dose of normal heart tissues, which has the potential benefit of reducing the risk of complications, such as ischemic heart disease, pericarditis/pericardial effusion, etc.

Objective:To analyze the influencing factors of hemoglobin changes in prostate cancer patients during radiotherapy combined with androgen-deprivation therapy (ADT) and analyze the relationship between the hemoglobin changes and long-term prognosis.Methods:The changes of hemoglobin levels in 145 prostate cancer patients treated with radiotherapy combined with ADT in Department of Radiation Oncology of Peking University First Hospital from November 2011 to May 2015 were retrospectively analyzed. Intensity-modulated radiotherapy (IMRT) was employed for conventionally fractionated radiotherapy. Luteinizing hormone-releasing hormone agonist was utilized for endocrine therapy.Results:The median hemoglobin reduction during radiotherapy combined with ADT was 8 g/L. The higher the baseline level of hemoglobin, pelvic irradiation and GS score before radiotherapy, the more obvious the decrease of hemoglobin during treatment (all P<0.001). Pelvic radiotherapy significantly increased the decline tendency of hemoglobin throughout the combined treatment (86.8% vs. 72.8%, P=0.05). The duration of endocrine therapy before radiotherapy and the hemoglobin changes during endocrine therapy alone were not significantly correlated with the degree of hemoglobin decline during subsequent radiotherapy ( P=0.53 and 0.837). The biochemical failure-free survival did not significantly differ between patients with significant and mild hemoglobin reduction ( P=0.686). Conclusions:The baseline level of hemoglobin before radiotherapy is negatively correlated with the decrease of hemoglobin during combined therapy. Pelvic radiotherapy is positively correlated with hemoglobin reduction during combined therapy. Hemoglobin reduction during combined therapy is not associated with the long-term biochemical failure-free survival of patients.

OBJECTIVE： To establish the method for the content determination of astragaloside Ⅳ， emodin and chrysophanol in Jianpi yishen pills （JYP） and to investigate the effects of JYP on calcium， phosphorus metabolism and inflammatory factors in chronic renal failure （CRF） model rats. METHODS： HPLC method was adopted. The determination of astragaloside Ⅳ， emodin and chrysophanol was perform on Agilent Zorbax SB-C18， Agilent TC C18 column， respectively； mobile phase consisted of acetonitrile-water （36 ∶ 64， V/V） and methanol-0.1％ phosphoric acid solution （75 ∶ 25， V/V）； the detectors were evaporative light-scattering detector and diode-array detector （detection wavelength of 254 nm）； the column temperatures were set at 30 ℃and 25 ℃ at the flow rate of 1.0 mL/min； the sample sizes were 20 and 10 μL. SD rats were randomly divided into normal group， model group， Niaoduqing group （1.80 g/kg） and JYP low-dose， medium-dose and high-dose groups （1.71， 3.43， 6.85 g/kg）， with 10 rats in each group. Except for normal group， CRF model of other groups were established by 5/6 nephrectomy in other groups. Four months after modeling， normal group and model group were given constant volume of water intragastrically； admi- nistration groups were given relevant medicine intragastrically， once a day， for consecutive 12 weeks. The levels of serum creatinine （Scr）， urea nitrogen （BUN）， parathyroid hormone （PTH） and inflammatory factors （IL-6， TNF-α） were measured by ELISA. Methyl thymol blue colorimetric method and phosphomolybdic acid method were used to detect the contents of blood calcium and phosphorus. Correlation of inflammatory factors with related calcium and phosphorus metabolism indexes （blood calcium， blood phosphorus， PTH） were investigated with Pearson assay. RESULTS： The linear range of astragaloside Ⅳ， emodin and chrysophanol were 54.537-381.759， 2.960-20.720， 6.318-44.223 μg/mL， respectively. The limits of quantitation were 0.010， 0.288， 0.216 μg/mL； the limits of detection were 0.003， 0.096， 0.072 μg/mL. RSDs of precision， reproducibility and stability tests were all lower than 3.0％. The recoveries were 97.18％-102.33％（RSD＜3％，n＝9）. After modeling （before medication）， serum contents of Scr and BUN in model group and administration group were increased significantly， compared with normal group （P＜0.01）. After medication， above indexes of administration group were decreased significantly， compared with model group and the same group before medication （P＜0.01）. Compared with normal group， the content of blood calcium were decreased significantly， while the contents of IL-6 and TNF-α were increased significantly （P＜0.01）. Compared with model group， the content of blood calcium were increased significantly in JYP medium-dose and high-dose groups， while serum content of PTH in Niaoduqing group， serum contents of PTH and IL-6 in JYP medium-dose and high-dose groups as well as serum content of TNF-α in administration group were decreased significantly （P＜0.05 or P＜0.01）. JYP had no significant effect on blood phosphorus in rats， and there was no correlation of inflammatory factors with related calcium and phosphorus metabolism indexes （P＞0.05）. CONCLUSIONS： The established content determination method is simple， specific and sensitive， and can be used for content determination of astragaloside Ⅳ， emodin and chrysophanol in JYP. JYP can improve renal function of CRF model rats， relieve calcium metabolism disorder and inhibit the expression of inflammatory factors.

OBJECTIVE： To optimize the water extraction technology of Bupi yangshen granules， and to provide basis for the follow-up research and development of it. METHODS： The contents of astragaloside Ⅳ and salvianolic acid B in water extract of Bupi yangshen granules， were determined by HPLC-ELSD and HPLC-DAD. Using the comprehensive score of contents of astragaloside Ⅳ and salvianolic acid B and extract yield as index， weight coefficient of indicators were determined by AHP， CRITIC and AHP-CRITIC mixed weighting method. L9（34） orthogonal test was used to optimize decoction time， water volume and decoction times in water extraction technology of Bupi yangshen granules. Validation test was also performed. RESULTS： The weight coefficient determined by AHP-CRITIC mixed weighting method was the most reasonable. The optimal extraction technology was decocting twice， adding 12-fold water， 1 h each time. The results of 3 times of validation test showed that the average contents of astragaloside Ⅳ and salvianolic acid B were 8.79， 609.50 mg （total amount of 121 g medicinal herbs extracted from whole prescription）， respectively. The average extract yield was 31.24％. Average comprehensive score was 96.59（RSD＝1.01％，n＝3）. CONCLUSIONS： The optimized water extraction technology is reproducible， stable and feasible. It can provide a scientific basis for the follow-up development and industrial production of Bupi yangshen granules.

Objective To analyze the adverse events in patients diagnosed with oligometastasized castration resistant prostate carcinoma (CRPC) receiving radiotherapy for the primary and metastatic prostate carcinomas.Methods Twenty patients with oligometastasized CRPC admitted to our hospital between 2011 and 2015 were treated with image-guided volumetric modulated arc therapy (VMAT).The dose for prostate+ seminal vesicle was 76 Gy/38 f,46 Gy/23 f for the pelvic lymph node and the median dose for the metastatic lesions was 60 Gy (52-66)/23 f.Relevant clinical data and adverse events were analyzed.Results All patients completed the radiotherapy.Only 1 patient showed grade Ⅲ urinary obstruction and received catheterization.In terms of acute adverse events of ≥ grade Ⅱ,urinary tract was observed in 4 cases (20％),rectum in 2 (10％) and blood system in 2(10％).The rectal V50 was correlated with acute adverse events of ≥ grade Ⅱ.The median follow-up time was 24.2 months.No patient suffered from late adverse events of ≥ grade Ⅱ.All cases showed a decline in the level of prostate specific antigen (PSA) after radiotherapy.The median PSA reduction rate was 99％.Among them,16 cases (80％) had a PSA reduction rate of over 90％.Conclusions It is safe and efficacious to perform radical dosage radiotherapy for primary and metastatic prostate carcinomas in patients with oligometastasized CRPC.

Objective To apply real-time transperineal ultrasound ( TPUS) to monitor the intra-fractional prostate motion,collect and analyze the data of the prostate motion,aiming to provide evidence for the optimization of the target area and plan of radiotherapy for prostate cancer. Methods TPUS is a non-invasive monitoring technique that utilizes an automatic scanning ultrasound probe to dynamically monitor and correct the motion of organs during radiotherapy. In this study, TPUS was utilized to collect 1588 intra-fractional data of 70 patients with prostate cancer. Prior to each cycle of radiotherapy,CBCT was adopted to correct the errors between intra-factional data by using VMAT. During radiotherapy, real-time ( once per second) ultrasound images were acquired to monitor the 3D motion of the prostate on the x (left+,right-),y (cranial+, caudal-), and z ( abdominal+, dorsal-) axes, emphasizing the analysis of 4D motion of the prostate. Results All patients successfully completed the treatment and data collection. The median time of effective monitoring per faction was 179 seconds (132-286 seconds). During 95% of the monitoring time,the distance of prostate motion was 2. 22 mm in the left direction,2. 17 mm in the right,2. 08 mm in the cranial, 1. 98 mm in the caudal,2. 44 mm in the abdominal and 2. 97 mm in the dorsal direction,respectively. In the x,y and z axes,the percentage of time in which the distance of prostate motion less than 1 mm among the total time was 83. 07%,85. 46% and 78. 27%,respectively,whereas 97. 70%,97. 87% and 96. 45% for＜3 mm, respectively. Conclusions TPUS is a non-invasive real-time monitoring technique,which can detect the 4D motion of the prostate during radiotherapy. By using VMAT,the range of prostate motion is relatively small, and the motion range is less than 3 mm in each direction within 95% of the time.