Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes from an open-label, dose-escalation, single-center, phase I/II clinical trial / 医学前沿

To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer (OMPC), we conducted a 3 + 3 dose escalation, prospective, phase I/II, single-arm clinical trial (CHiCTR1900025743), in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy, comprising intensity modulated radiotherapy to the pelvis, and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4-7 weeks, at 39.6, 45, 50.4, and 54 Gy. Robotic-assisted radical prostatectomy was performed after 5-14 weeks. The primary outcome was treatment-related toxicities and adverse events; secondary outcomes were radiological treatment response, positive surgical margin (pSM), postoperative prostate-specific antigen (PSA), pathological down-grading and tumor regression grade, and survival parameters. Twelve patients were recruited from March 2019 to February 2020, aging 66.2 years in average (range, 52-80). Median baseline PSA was 62.0 ng/mL. All underwent RARP successfully without open conversions. Ten patients recorded pathological tumor down-staging (83.3%), and 5 (41.7%) with cN1 recorded negative regional lymph nodes on final pathology. 66.7% (8/12) recorded tumor regression grading (TRG) -I and 25% (3/12) recorded TRG-II. Median follow-up was 16.5 months. Mean radiological progression-free survival (RPFS) was 21.3 months, with 2-year RPFS of 83.3%. In all, neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.

Comparisons of dose distributions between IMPT and VMAT for pancreatic cancer / 中华放射医学与防护杂志

Objective:To compare dose distributions of hypofractionated radiotherapy for pancreatic cancer between IMPT and VMAT.Methods:Ten pancreatic cancer cases were included in this retrospective study. Photon (Edge) and proton (Proteus?PLUS) plans were designed by Eclipse and RayStation TPS, respectively. All plans were transferred to MIM system for extraction of parameters, which included Dmin, Dmean and Dmax of PTV, conformity index (CI), new conformity index (nCI), homogeneity index (HI), gradient index (GI), coverage, Dmax and dose-volume of the organs at risk (OARs). Results:There was no significant difference in CI between the two groups. The higher PTV Dmin, Dmean, Dmax, D98%, D2%, HI, coverage and the better GI, D2 cmwere found in VMAT ( t/ Z=-4.63-5.32, P<0.05). The lower 10%_PD was found in IMPT ( t=-7.47, P<0.05). Regarding the OARs, Dmax of the intestine, stomach, and duodenum and Dmean of the left kidney were similar between two groups without significant difference ( P>0.05). The D5 cm 3 of the intestine, D10 cm 3 of the stomach, D5 cm 3 and D10 cm 3 of the duodenum, D2/3 of the left kidney, Dmean and D2/3 of the right kidney were lower in IMPT than those in VMAT ( t/ Z=-8.12--2.60, P<0.05). However, the Dmax and D0.35 cm 3 of the spinal cord were higher in IMPT than those in VMAT ( t=7.30, 6.77, P<0.05). Conclusions:Both of hypofractionated radiotherapy plans of pancreatic cancer designed by VMAT and IMPT could meet clinical needs. No significant difference was found in Dmax of the adjacent gastrointestinal tracts between the two groups. While IMPT had the advantage over VMAT in the case of lower dose-volumes of the gastrointestinal tracts. Nevertheless, less protections of the OARs in front of the tumor volume could be provided by IMPT compared with VMAT.

Comparison of dose distributions among five radiotherapy apparatuses in stereotactic body radiation therapy for pancreatic cancer / 中华放射肿瘤学杂志

Objective:To compare the dose distribution among CyberKnife, Tomotherapy, Edge, Triology and γ-knife in stereotactic body radiation therapy (SBRT) for pancreatic cancer.Methods:Clinical data of 10 panreatic cancer patients receiving CyberKinife treatment were retrospectively analyzed. The treatment plans were designed by five apparatuses from five centers according to the uniform requirement. All plans were transferred to MIM system for the extraction of parameters, which mainly included D min, D mean and D max of PTV, conformity index (CI), new conformity index (nCI), homogeneity index (HI), gradient index (GI), coverage, D max and dose-volume of the stomach and bowel. Results:The best CI and nCI were obtained in Triology ( P<0.001), and the worst HI was found in γ-knife ( P<0.001). The best GI was found in CyberKnife, followed by γ-knife and Tomotherapy, and Edge showed the worst GI ( P<0.001). The highest D min of PTV was found in both Edge and Triology, while lower D min of PTV was found in CyberKnife and Tomotherapy ( P<0.001). Additionally, γ-knife provided the highest D mean and D max of PTV ( P<0.001). Regarding the organs at risk, the lowest D max and D 5cm 3 of the bowel ( P<0.001), D max of the stomach ( P=0.003), D max( P=0.001), D 5cm 3 ( P<0.001) and D 10cm 3 ( P=0.005) of the duodenum, D max( P<0.001) and D 0.35cm 3 ( P<0.001) of the spinal cord were found in CyberKnife. The highest D max of the bowel was found in γ-knife. Furthermore, the highest D 5cm 3 of the duodenum was demonstrated in Edge ( P<0.001) and Tomotherapy provided the highest D max( P<0.001) and D 0.35cm 3 of the spinal cord ( P<0.001). Conclusions:All five radiotherapy apparatuses can meet the requirement of SBRT for pancreatic cancer. More rapid dose fall-off could be obtained via CyberKnife and γ-knife. Triology and Edge provide better target conformity. CyberKnife can better protect the gastrointestinal tract.

Research on immunophenotype of primary pancreatic cancer / 中华胰腺病杂志

Objective To comprehensively analyse the immunophenotype of primary pancreatic cancer,providing biological clues for treating pancreatic cancer.Methods The genome nap of 177 primary pancreatic cancer patients from the Cancer Genome Atlas (TCGA) database were enrolled.The overall immune infiltration score (IIS),T cell infiltration score (TIS) and antigen presenting machinery (APM) score were quantified for each specimen.By using unsupervised clustering,the patients were divided into immune-high group and immune-low group according to IIS,TIS,and APM scores.The differences on the inffiltration of immune cell subtype,expression of immune checkpoint and immunological function evaluation were compared between two groups.Results In the radiotherapy population,the survival rate of immune-high group was slightly higher than that of immune-low group with no statistical significance.The immune-high group had more infiltrated neutrophils (63.4％ vs 36.6％),eosinophils (75.5％ vs 24.5％),activated CD4 + memory T lymphocytes (80.7％ vs 19.3％),naive CD4 + T lymphocytes (81.2％ vs 18.8％) and naive B lymphocytes (59.5％ vs 40.5％) compared with immune low group;while the immune-low group had more activated NK cells (67.3％ vs 32.7％),regulatory T lymphocytes (68.9％ vs 31.1％),T follicular helper (67.7％ vs 32.3％),and activated mast cells (62.9％ vs 37.1％).Co-stimulatory molecules such as CD28,ICOS,CD40,CD40L,CD27,CD27L,4-1BB,OX40,GITR and co-inhibitory molecules including CTLA-4,PD-L2,PD-1,VISTA,LAG-3,TIGIT,Galectin-9,TIM-3,and IDO-1 were significantly higher expressed in the immune-low group (all P ＜ 0.05).The PC1 value of principal component analysis of chemokine expression levels and the cytolytic activity (CYT) in the immune-high group were significantly higher (all P ＜0.001).Conclusions Clustering on the three inmune quantification scores could be preliminarily used for immunophenotyping pancreatic cancer.The immune-high group may have synergistic effect with radiation therapy.Treatment with immune checkpoint inhibitor may be effective in immune-low group.

Effect of stereotactic body radiation therapy on the survival of patients with pancreatic cancer recurrence after surgery / 中华胰腺病杂志

Objective To identify the effect of stereotactic body radiation therapy (SBRT) on the survival of patients with recurrent pancreatic cancer after surgery.Methods The data of 104 patients with recurrent pancreatic cancer after surgery who underwent SBRT in the Department of Radiation Oncology of Changhai Hospital,Navy Medical University from February 2012 to December 2016 were retrospectively analyzed.The prescription doses ranged from 35-40 Gy/4-8 f.Survival analysis was performed using the Kaplan-Meier method,and relevant factors affecting patients' survival were screened by the Cox proportional hazards model.Results The median overall survival (OS) and progression free survival (PFS) was 12.5 (11.0-14.0) months and 7.3 (6.0-8.7) months,respectively,while the 1-year rate of OS and PFS was 55.8％ and 22.1％,respectively.Multivariate analysis indicated that tumor stage,biological effect dose (α/β =10,BED10),the decrease of CA19-9 level after treatment,and follow-up chemotherapy were all related factors affecting overall survival;tumor stage,BED10,the degree of pain relief and the decrease of CA19-9 level after treatment were related factors affecting PFS.Conclusions Patients suffering recurrent pancreatic cancer with early tumor stage,normal CA19-9 level and mild pain before treatment could be better treated by SBRT,BED10 ≥60 Gy and follow-up chemotherapy after radiotherapy can prolong the survival of patients.

Influence of stereotactic body radiation therapy on the survival of patients with early stage pancreatic cancer / 中华胰腺病杂志

Objective To evaluate the efficacy of stereotactic body radiation therapy (SBRT) on the survival of patients with early stage pancreatic cancer.Methods The clinical data of 103 T1-2N0M0 pancreatic cancer patients treated by CyberKnife SBRT at the Department of Radiation Oncology of Changhai Hospital from January 2012 to December 2016 was retrospectively analyzed.Kaplan-Meier method was used for survival analysis and Cox proportional hazards model was utilized to identify survival related factors.Results The median overall survival(OS) of T1-2N0M0 pancreatic cancer patients who had unresectable pancreatic cancer or refused surgery was 17.7 (16.1-19.3) months.1-year and 2-year OS rate were 86.3％ and 24.6％,respectively.The median progression free survival(PFS) was 13.0(10.7-15.3) months.1-year and 2-year PFS rate were 54.5％ and 6.3％,respectively.Patients with chemoradiation,BED10 ≥60 Gy and CA19-9 decrease ＞ 50％ after treatment had longer OS and PFS.Conclusions SBRT is a safe and effective treatment for patients with T1-2N0M0 pancreatic cancer.

The study on the parameters of treatment plans for pancreatic cancer with cyber-nife system / 中华胰腺病杂志

[Abstact] Objective To analyze the related parameters of the treatment plans for the pancreatic cancer with the Cyber-knife system.Methods The clinical data of 129 patients with single-target pancreatic cancer for the first time who underwent CyberkKnife radiosurgery between January 2017 and December 2017 in Shanghai Changhai Hospital were retrospectively analyzed.The parameters were all selected from the MultiPlan @4.0.2 treatment planning system and the data were analyzed.Results The volume of the targets in 129 patients with pancreatic cancer was 3.355-238.936 cm3,with the average volume of 51.43 ± 55.64 cm3.Patients were averagely treated for 5 to 8 sessions,and the average prescription dose was 6 Gy × 6 fraction,which equaled to 58 Gy in the biological equivalent dose (BED).The collimators with 20 mm and 15 mm accounted for up to 31％ and 27％,respectively,which were the top 2 options.The finally designed the conformal index(CI),new conformal index(nCI),and the homogeneity index were 1.14 ± 0.09,1.29 ± 0.09 and 1.42 ± 0.04,respectively.The coverages of tumor target was 80.3％-95.6％,with the average of 90.0 ± 4.6％.The treatment nodes,beams and Mus are 79,180 and 7 060 in average.The estimated treatment time was 42 ± 8 minutes.The organs at risk can be protected very well.Conclusions Reasonable Cyber-knife treatment plan can guarantee that stereotactic body radiation therapy can effectively treat Pancreatic Cancer.

The value of DWI in monitoring therapeutic effects of Cyberknife on pain for locally advanced pancreatic cancer / 中华胰腺病杂志

Objective To evaluate the short-term therapeutic efficacy of Cyberknife in alleviating the pain of locally advanced pancreatic cancer (LAPC) and explore the application of DWI in the pain evaluation.Methods Visual analogue scale (VAS) and Quality of life score KPS were conducted in 36 LAPC patients before and 1 month,3 month after radiotherapy,who underwent conventional MRI examination and DWI scan.The changes of VAS and KPS scores were observed before and after the treatment,as well as the apparent diffusion coefficients (ADC) changes of region of interest (ROI) in the DWI images,and the correlation of ADC with KPS and VAS was analyzed.Results VAS before and at 1 month and 3 month after the treatment was (4.89 ± 2.89),(1.08 ± 2.06) and (0.51 ± 1.48).KPS before and at 1 month and 3 month after the treatment was (72.47 ± 14.74),(93.33 ± 10.69) and (92.86 ± 10.73).ADC of DWI before and at 1 month and 3 month after the treatment was 1.47 ± 0.28,1.79 ± 0.33 and 1.94 ± 0.41,and the differences were statistically significant (all P values ＜0.001).VAS was obviously decreased at 1 month and 3 month after the treatment,while KPS and ADC were greatly increased,and the differences were statistically significant (P value ＜ 0.05).There was no statistical difference between those at 1 month and those at 3 month.There was no obvious correlation between ADC and VAS and KPS at 1 month and 3 month after the treatment.Conclusions After Cyberknife treatment,the pain was obviously relieved and the life quality was greatly improved within short period,but ADC of DWI can not sensitively monitor the changes of the pain.

Analysis on the therapeutic effects of re-irradiation with stereotactic body radiation therapy for the advanced recurrent locally pancreatic cancer / 中华胰腺病杂志

Objective To investigate the safety and efficacy of re-irradiation with stereotactic body radiotherapy(SBRT) for treating locally recurrent advanced pancreatic cancer.Methods From 2014 to 2017,7 patients with stage Ⅲ pancreatic cancer were treated by re-irradiated with SBRT at Shanghai Changhai Hospital.SBRT was delivered via the G4 type cyberknife robotic stereotactic radiosurgery system in all the patients.The median dose of the first SBRT was 35Gy/5-7 fx,and the median dose of re-irradiation with SBRT was 31 Gy/5-8 fx.6 patients had undergone sequential chemotherapy either with gemcitabine or S-1 based therapy except one patient who refused the chemotherapy.Results There were 5 male and 2 female patients.The median overall survival (OS) of 7 patients was 30 months.Patients were re-irradiated with SBRT after a median interval of 10 months after the first SBRT.Median OS and locally relapse-free survival (LFRS) from re-irradiation were 13 months and 11 months,respectively.Three months after re-irradiation,3(42.9％) patients had partial remission and 4 patients had stable disease.Pain disappeared in 4 patients at the end of reirradiation and significant pain was alleviated in 2 patients 1 month after re-irradiation.There were no toxicities of grade 3 or higher grade during two courses of SBRT.Conclusions For patient with locally recurrent advanced pancreatic cancer,SBRT re irradiation regimen was associated with acceptable toxicity,which can effectively alleviate the pain,prolong the survival and improve the life quality.

Efficacy and safety of stereotactic body radiation therapy for very elderly patients with pancreatic cancer / 中华胰腺病杂志

Objective To investigate the efficacy and safety of stereotactic body radiation therapy (SBRT) for very elderly patients with pancreatic cancer.Methods The clinical data of a total of 149 patients aged from 75 to 90 years with locally advanced or metastatic pancreatic cancer treated by SBRT in Changhai Hospital from January 2012 to December 2016 were retrospectively reviewed.Prescription doses ranged from 3.6-9Gy/fractions,and the total doses were 19.5-49Gy in 3-8 fractions.The level of serum cancer antigen 19-9(CA19-9) before and 3 months after treatment was compared and the radiotherapy biological effective dose (BED10) was calculated.The adverse events of the radiotherapy were observed.Overall survival (OS) and progression-free survival (PFS) were recorded through follow-up,and the factors influencing the patients' survival were investigated by univariate and multivariate analysis.Results All the patients' median OS and PFS were 12.9and 8.3 months,respectively.One-year OS and PFS rate were 55.9％ and 19.5％,respectively.Tumor stage and the decrease of CA19-9 levels ＞50％ at 3 months after treatment and BED10 were independent factors of OS and PFS.No grade 3 or higher toxicities were recorded in all the patients.Conclusions SBRT is safe and effective for very elderly patients with locally advanced or medically inoperable pancreatic cancer.Tumor stage,the decrease of CA19-9 levels after treatment and BED10 were associated with prognosis.

Organ endangering dose and side effects in two courses of stereotactic body radiation therapy for pancreatic cancer / 中华胰腺病杂志

Objective To assess the cumulative doses and side effects after two courses of stereotactic body radiation therapy (SBRT) for pancreatic cancer. Methods Twenty-four pancreatic cancer patients who received two courses of SBRT were enrolled. Organ endangering dose accumulations were calculated by rigid and non-rigid registration. All doses were recalculated to an equivalent dose of 2 Gy per fraction. Results The median of accumulated maximal dosage (Dmax) and dosage per 1cc(D1cc) of the stomach,duodenum and the bowel were 43.87 and 35.28 Gy 3,35.53 and 26.59 Gy3,45.08 and 36.18 Gy3; and the median volume under the dosage of 10Gy (V10) was 107.40,23.98 and 169.26cc, respectively. The median accumulated Dmaxand the dosage of 35% volume(D0.35) of the spinal cord was 8.42 and 7.83Gy3. The median cumulative Dmeanand D2/3of the left and right kidney were 5.18 and 3.65 Gy3, 3.50 and 2.57 Gy3, respectively. The median cumulative Dmeanand D50%of the liver was 5.18 and 3.64Gy3,respectively. The median summed dose to the overlapping radiation field of the two courses was 93.38 Gy3. No grade 3-4 toxicity occurred. Conclusions The cumulative doses to organs at risk as dose constraints were safe and acceptable,which could be used as a reference to evaluate whether a second SBRT could be done after initial SBRT for pancreatic cancer.

The application of different Auto-shells and optimization steps of CyberKnife treatment plans for pancreatic cancer / 中华胰腺病杂志

Objective To propose the method of dose distribution calculated by one-step optimization with 7 shells (Cao method) and compare with that by three-step optimization with 4 shells (Blanck method) and CyberKnife treatment plans for pancreatic cancer. Methods 20 cases of pancreatic cancer who underwent CyberKnife treatment were retrospectively analyzed,and CT was performed to localize and delineate the target area and endangering organs. Dosage was optimized and evaluated with Blanck method and Cao method. The planning target volume (PTV) conformity index (CI), new conformity index (nCI), homogeneity index (HI),gradient index (GI), coverage, dose-volume and doses to organs at risk were compared. Results Compared with Blanck method, CI (1.11 ± 0.05 vs 1.15 ± 0.05), nCI (1.20 ± 0.06 vs 1.23 ± 0.06), coverage [(92.48 ± 1.85)% vs (93.53 ± 2.15)%], volumes encompassed by 100% and 30% prescription dose line (36.46 ± 16.64 vs 38.19 ± 17.68; 286.19 ± 126.52 vs 320.93 ± 154.82) and monitor unit (56 369 ± 20 019 vs 57 814 ± 20 531) were significantly decreased,while GI was increased (3.22 ± 0.19 vs 3.11 ± 0.19), and all the differences were statistically significant (P<0.05). Additionally, Dmax of the intestine (21.17 ± 2.90 vs 20.63 ± 3.13), D10cc of the stomach (12.78 ± 2.57 vs 13.11 ± 2.43), D5ccof the duodenum (11.01 ± 3.45 vs 11.50 ± 3.25), D10ccof the duodenum (9.30 ± 3.31 vs 9.78 ± 3.07) and D0.35ccof the spinal cord (6.09 ± 0.98 vs 6.59 ± 0.92) were all significantly decreased (P<0.05). No significant differences were found on other parameters. Conclusions Better dose distributions are accessible by one-step optimization with 7 shells in CyberKnife treatment plans for pancreatic cancer.

Research advances in tumor radiosensitization mediated by topoisomerase inhibitors / 中华放射医学与防护杂志

As anticancer drugs,topoisomerase inhibitors have been widely used in clinical practice,and their radiosensitivity has been gradually recognized.Many topoisomerase inhibitors are currently in pre-clinical and clinical studies.Several studies have shown that some topoisomerase inhibitors may be potential ideal radiosensitizers.However,the physico-chemical properties,toxicity and sensitization effects should be further investigated.

Prognostic value of ADCtot for overall survival of patients with locally advanced pancreatic cancer receiving CyberKnife followed by sequential S-1 / 中华胰腺病杂志

Objective To explore the prognostic value of ADC tot of diffusion-weighted magnetic resonance imaging with multiple diffusion gradient factor ( b) values ( Mb DWI) in predicting overall survival (OS) of patients with locally advanced pancreatic cancer (LAPC) undergoing CyberKnife and sequential S-1. Methods Forty-one LAPC patients were enrolled (28 male and 13 female), who had routine pancreatic MRI and multiple b value DWI (Mb DWI, b value =0, 25, 50, 75, 100, 150, 200, 400, 600, 800 and 1000 s/mm2) scan (3.0 T) prior to radiotherapy.ADCtot value was calculated using single index model .Two independent radiologists on abdominal radiology manually drew the target area of interest and measured ADC tot at 1-month interval, and the interclass correlation coefficient (ICC) was calculated.The median ADCtot was used as a standard to divided the data into high value and low value .The survival was analyzed by Kaplan-Meier method and compared by log rank test .Cox proportional hazard model was employed to identify predictive factors for OS.Results The median ADCtot value by two independent radiologists was (1.54 ±0.27) ×10 -3 and(1.55 ±0.28) ×10 -3 mm2/s, respectively.The ICC was 0.994, and the consistency was good.Pre-treatment ADC tot value was the independent prognostic factor for the OS of patients who received CyberKnife and S-1 (HR: 1.083, 95％CI 1.083-12.554,P=0.0368), indicating that the mortality increased by 1.083 times as ADCtot increased by 1 unit.Similarly, CyberKnife combined with S-1 was also the independent prognostic factor for the OS (HR:0.329, 95％CI 0.142-0.765, P=0.0098), indicating that the mortality of patients treated by CyberKnife and S-1 was 0.329 times of that of patients who did not take S-1. Conclusions The pre-treatment ADC tot was an independent predictor for OS of LAPC patients treated by CyberKnife and sequential S-1, which had a certain prognostic value .

Influence of combined treatment sequence of stereotactic body radiation therapy and chemotherapy on the survival of very elderly patients with locally advanced pancreatic cancer / 中华胰腺病杂志

Objective To investigated the influence of different combined treatment sequence of stereotactic body radiation therapy (SBRT) and chemotherapy (CT) on the survival of very elderly patients with locally advanced pancreatic cancer ( LAPC) .Methods The data of LAPC patients ≥60 years old treated by CyberKnife SBRT at Shanghai Changhai Hospital from January 2012 to December 2016 was retrospectively analyzed.According to treatment sequences , patients were divided into three groups:CT+SBRT group ( first chemotherapy and then SBRT ) , SBRT+CT group ( first SBRT and then chemotherapy ) and CT+SBRT+CT group ( first chemotherapy , then SBRT and finally chemotherapy ) .Patients were recommended to receive a 6-month chemotherapy .Intravenous administration of 1000 mg/m2 gemcitabine was initiated on day 1, 8, and 15 every 4 weeks or S-1 was orally given at a dose of 80 mg/m2 for 28 days followed by a 14-day rest , which repeated for 6 cycles.Radiotherapy parameters: the median total prescription dose was 36(30-45)Gy; the median per fraction dose was 7(5-9)Gy;the median number of fractions was 5(5-8) fractions;the median biological equivalent dose (BED10) were 61.92(48-85.5) Gy, respectively.The interval between SBRT and chemotherapy ranged from 2 to 3 weeks.Patients were followed every 3 months.The main outcome measures were overall survival ( OS) and median progression free survival ( PFS) .Second outcome measure was adverse events.Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) was employed to evaluate adverse events , and RTOG/EORTC was used to assess the adverse events of radiotherapy .Overall survival (OS) and PFS were calculated by Kaplan-Meier method.Univariate and multivariate logistic regression model were used to analyze the independent risk factors .Results A total of 260 patients were enrolled in the study , including 28 patients treated with CT+SBRT, 163 patients undergoing SBRT +CT and 69 patients treated with CT+SBRT+CT.The median OS and PFS were 13.2(95％CI 12.8-13.6)months and 8.2(95％CI 7.7-8.7)months, respectively.OS in CT +SBRT, SBRT +CT and CT +SBRT +CT group was 12.2 (10.9-13.9),13.4 ( 12.9-13.9 ) and 13.1 ( 12.7-13.5 ) months, and the differences were not statistically significant(P=0.425).PFS in CT+SBRT, SBRT+CT and CT+SBRT+CT group was 6.4(5.9-6.9), 8.3(7.8-8.8) and 8.2(7.2-9.2)months, and the differences were statistically significant (P=0.008).In univariate analysis , ECOG, SIRI, the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In multivariate analysis, the CA19-9 response and BED10 were independent factors for OS . Multivariate analysis showed that the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In CT+SBRT group, patients had lower ECOG score (χ2 =115.325,P<0.001) and earlier clinical staging (χ2 =24.788, P<0.001 ).In SBRT +CT group, patients had advanced staging (χ2 =159.759,P<0.001) and lymph node metastasis(χ2 =40.925,P<0.001).Only 1 patient experienced grade 3 radiotherapy associated duodenitis .The adverse events of patients who were first treated by chemotherapy included grade 3 neutropenia in 4 patients and grade 3 gastrointestinal reaction in 5 patients.The adverse events of patients who were first treated by radiotherapy included grade 3 neutropenia or/and leucopenia in 18 patients and grade 3 abdominal pain, nausea or vomit in 16 patients.The adverse events of CT +SBRT+CT patients included grade 3 neutropenia or/and leucopenia in 4 patients and grade 3 abdominal pain or nausea in 5 patients.There was no grade ≥4 adverse events.Conclusions For very elderly patients with LAPC , the survival of patients who received pre-SBRT chemotherapy , post-SBRT chemotherapy and pre-and post-SBRT chemotherapy was comparable , but SBRT+CT group and CT +SBRT+CT group had longer PFS than CT +SBRT group.

The optimization of enhancement scanning delay with CT-based simulation before cyberknife treatment for pancreatic cancer / 中华放射医学与防护杂志

Objective To assess the optimal delay time of enhanced scanning with CT-based simulation before cyberknife treatment for pancreatic cancer and to analyze the correlations between the target delineation and the rating items.Methods One hundred and twenty pancreatic cancer patients underwent Philips 16 big core spiral CT before cyberknife treatment.Patients were assigned to three groups randomly with scan delays of 25,45 and 65 s;30,50 and 70 s;and 35,55 and 75 s respectively.After the scanning,the images were evaluated by three associate professors in the field of radiation oncology.To achieve the optimal delay time,the data were compared with a random intercept model of mathematical mean,the Sidak method and One-way ANOVA.Pearson method was used to analyze the correlations between the target delineation and the rating items.Results The tumor boundaries,retroperitoneal lymph nodes,duodenal images,accuracy of target volume delineations in 45 and 65 s,50 and 70 s,55 and 75 s items rating difference had no statistically significant differences (P ＞ 0.05),but significantly superior to those in 25,30,35 s groups respectively(t =3.59-21.68,13.34-15.46,12.42-13.83,P ＜0.05).Therefore,the proposed delay time interval was 50-65 s,and the average value of the target volume delineation was the highest in 55 s group (3.91-± 0.50).When the scan delay time was 55 s,the target delineation was positively correlated with the tumor boundary (r =0.914 4,P ＜ 0.05),and negatively related to the value of other imaging (r =-0.926 3,P ＜ 0.05).Conclusions The recommended delay time interval of pancreatic cancer before cyberknife treatment CT enhanced scanning was 50-65 s,and the optimal time point was 55 s.The target volume delineation was positively correlated with the boundary of the tumor,and significant negatively related to the value of other imaging.

The application of CyberKnife stereotactic body radiotherapy in treatment of oligometastatic prostate cancer / 中华泌尿外科杂志

Objective To determine the effectiveness and safety of stereotactic body radiotherapy (SBRT)-CyberKnife for oligometastatic prostate cancer.Methods From May 2012 to February 2017,31 patients treated by CyberKnife were retrospectively reviewed,with a median age of 67 years(range 52 to 83 years),including 50 oligometastatic and 2 primary prostate cancer patients.The median PSA level was 8.4 ng/ml(range 0 to 300.0 ng/ml) and PSA test was performed every month.PSA progression-free survival (PSA-PFS),time to initiation of androgen deprivation therapy (ADT) and local control rate (LCR) were measured as the main outcomes.Results SBRT was well tolerated and were performed as planned in all patients.No SBRT related acute or late toxicities were observed.No bone fracture was observed in patients treated by bony targeted radiotherapy.The median follow-up after SBRT was 20.7.months (range 1.2-58.3 months).The median PSA-PFS was 5.3 months (range 0-58.3 months).1-year,2-year,and 4-year PSA-PFS was 52.0％,36.7％ and 36.7％ respe ctively.PSA level decrease was observed in 21 oligometastatic prostate cancer patients after SBRT,with median PSA-PFS of 12.3 months (range 1.2-58.3 months).PSA level increase was observed in 29 oligometastatic prostate cancer patients after SBRT.Six local recurrence were observed resulting in an actuarial 1-year,2-year and 3-year LCR of 90.4％,86.9％ and 82.6％,respectively.Twelve patients treated without ADT after SBRT,with median follow-up of 8.6 months (range 2.9-58.3 months) in this subgroup.Seven patients were added ADT after SBRT,with the median time from SBRT to initiation of ADT of 13.3 months (range 3.0-24.0 months) in this subgroup.Twelve patients were treated with ADT continuously after SBRT.Conclusions CyberKnife seems to be a safe and effective treatment with tolerated adverse events and good local control for patients with oligometastatic prostate cancer.

The optimization of CT localization enhanced scan time of pancreatic cancer in different positions before cyberknife treatment / 中华胰腺病杂志

Objective To explore the optimal delay time of enhanced scanning with CT based simulation before cyberknife treatment of carcinoma in different positions of the pancreas.Methods Philips 16 large aperture spiral CT scan was applied.Fifty-three patients with carcinoma in the head of the pancreas and 60 pancreatic cancer patients in the body or tail were randomly assigned to three groups with scan delays of 25,45,and 65 seconds in group A (25s group,pancreatic head n =18,pancreatic body or tail n =21);30,50,and 70 seconds in group B (3 0s,pancreatic head n =17,pancreatic body or tail n =19);and 35,55,and 70 seconds in group C (35s,pancreatic head n =18,pancreatic body or tail n =20),respectively.Images were evaluated by three associate professors of radiation oncology based on image quality score scale.The items rating in different time points were compared using a random intercept model of mathematical mean in three groups.Then the items rating of different time points were compared in pairs using the Sidak method.One-way ANOVA was used to compare the optimal time point of each group,so the optimal delay time of enhanced scanning with CT based simulation before cyberknife treatment of pancreatic cancer was obtained.Results The delayed time points with the highest scores for target delineation of the tumor in the pancreatic head and the pancreatic body or tail by CT enhanced scanning in three groups were 45 s/65 s,50 s/50 s,55 s/75 s,respectively.There was no significant difference in the scan time of 45 s,50 s and 55 s for the tumor in the pancreatic head.Similarly,no significant difference could be found in the scan time of 65 s,50 s and 75 s for the tumor in the pancreatic body and tail.Conclusions The recommended delay time interval for localizing the tumor in pancreatic head by CT enhanced scanning was 45 ～ 55 s,and for the tumor in the pancreatic body or tail was 50 ～75 s.

An initial report of CyberKnife stereotactic body radiotherapy in treatment of small hepatocellular carcinoma:a pilot study / 中华放射医学与防护杂志

Objective To determine the effectiveness and safety of patients treated with stereotactic body radiotherapy ( SBRT ) - CyberKnife for small hepatocellular carcinoma. Methods A prospective analysis of treatment details and outcomes for 33 patients with small hepatocellular carcinoma treated by CyberKnife at CyberKnife center of Shanghai Changhai Hospital from June 2014 to December 2016 was presented. Patients were followed every 3 months. WHO modified response evaluation criteria in solid Tumors( mRECIST) was used to evaluate efficacy, Common Terminology Criteria for Adverse Events Version 4. 0(CTCAE 4. 0) to evaluate treatment response, Kaplan-Meier method to calculate survival rate and local control rate and plot survival curves. Results There were 33 patients, 33 targets included in the study at the date of the last follow-up. 18 lesions (54. 5%) showed complete remission response, 7 lesions (21. 2%) showed partial remission response, 5 lesions (15. 2%) showed stable, and 3 lesions (9. 1%) progressed. Response rate was 75. 8%, and disease control rate was 90. 9%. 1- and 2-year local control rate was 100% and 83. 6%, respectively. The median disease progression free survival ( DPFS) was 15. 0 months. Non irradiated liver volume more than 100 ml, prior AFP less than 100 ng/ml, post-treatment CTCAE less than grade 2 could improve overall survival ( OS ) . V5 was a factor in grades 2 -4 hepatic toxicity ( P=0. 015 ) . All patients tolerated the radiosurgery, with grade 1 and grade 2 fatigue, and the gastrointestinal reactions and liver injury was the main side effect. 1 patient with grade 3 liver damage relieved at 6 months after treatment and 1 patient with grade 4 liver damage cured at 12 months after treatment. No grade 5 toxicity was encountered. Conclusions CyberKnife seems to be a safe and effective treatment measure with tolerated adverse reaction and good local control rate for patients with small hepatocellular carcinoma.

The application of multiple b value DWI in evaluating the short-term efficacy of cyberknife for locally advanced pancreatic cancer / 中华胰腺病杂志

Objective To explore the value of Multiple b value DWI ( MbDWI ) in the short-term efficacy evaluation of cyberknife radiotherapy for locally advanced pancreatic cancer ( LAPC ) .Methods A total of 36 patients underwent both conventional sequence and respiratory triggered MbDWI ( b=0, 25, 50, 75, 100, 150, 200, 400, 600, 800, 1 000 s/mm2 ) before cyberknife radiotherapy, 1month and 3 months after the radiotherapy, respectively.ADCtot, f, Dfast and Dslow were calculated using single and double exponential model and the changes before and after radiotherapy were observed.Results Before radiotherapy, 1 month and 3 months after radiotherapy, the ADCtot values of solid lesions were (1.56 ±0.29) ×10-3 mm2/s, (1.75 ±0.31) ×10 -3 mm2/s and (18.6 ± 0.46) ×10 -3 mm2/s;the values of Dslow were (1.10 ±0.73) × 10 -3 mm2/s, ( 1.19 ±0.97 ) ×10 -3 mm2/s and ( 1.49 ±04.6 ) ×10 -3 mm2 s/; the values of Dfast were (83 .33 ±62 .57) ×10 -3 mm2/s,(124.57 ±123.10) ×10 -3 mm2/s and (108.07 ±96 .67) ×10 -3 mm2 /s; f values were (26.81 ±23.74)%,(23.61 ±22.75)% and (21.34 ±15.36)%, respectively.ADCtot values 1 month and 3 months after treatment were significantly higher than those before treatment and Dslow 3 months post-treatment was higher than that before treatment, and the differences were statistically significant ( both P<0.05) and no other differences between two groups were significant.There were no statistical differences on Dfast and f before and after radiotherapy.Conc lusions ADCtot and Dslow both showed a significant growth trend after cyberknife radiotherapy.The advanced degree of parenchymal cystic in the targeted lesion could reflect the short-term efficacy of cyberknife treatment.