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.

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.

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.

Pseudolaric Acid B Inhibits Proliferation, Invasion and Epithelial-to-Mesenchymal Transition in Human Pancreatic Cancer Cell

PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.

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.

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.

Relationship between the peripheral dose and radioactive counts of 125I seeds detected by SPECT/CT / 中华核医学与分子影像杂志

Objective To explore the relationship between the peripheral dose and radioactive counts of 125I seeds detected by SPECT/CT.Methods Six 125I seeds(1.48×107 Bq, 1.85×107 Bq, 2.22×107 Bq, 2.59×107 Bq, 2.96×107 Bq, 3.33×107 Bq) were put into the solid water phantoms respectively. SPECT/CT was applied to scan the seeds. The radioactive counts (x) at the distance of 1-15 mm from the center of seeds were recorded respectively, while the corresponding doses (y, cGy) were calculated. SPSS 18.0 was used to analyze the relationship between the radioactive counts and peripheral dose. Results There was an exponential relationship between the peripheral dose of 125I seeds and the radioactive counts. The formula was as follow: y=507.849×1.004x. Conclusion SPECT/CT can visualize the peripheral dose of 125I seed, which may provide a method for dosimetric verification after brachytherapy.

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.

125I seed implantation for retroperitoneal lymph node metastasis caused by recurrent cervical cancer after radiotherapy: preliminary results / 介入放射学杂志

Objective To evaluate the safety and efficacy of CT-guided radioactive 125I seed implantation in treating retroperitoneal lymph node metastasis due to recurrent cervical cancer after radiotherapy.Methods A total of 10 patients with retroperitoneal lymph node metastasis (12 lesions in total)due to recurrent cervical cancer after radiotherapy,who were treated with CT-guided 125I seed implantation during the periodfrom November 2011 to October 2015,were included in this study.The diameters,that were perpendicular to each other,of the involved lymph nodesranged from 1.7 cm×1 cm to 6.5 cm×5 cm,the diameter of 6 involved lymph nodes (50％) was ＜5.0 cm and the diameter of other 6 involved lymph nodes (50％) was ≥5.0 cm.With the help of treatment planning system for brachytherapy,the source distribution was formulated.Under CT guidance,the 125l seedswith the activity of 0.3-0.7 mCi were implanted.Postoperative validation showed that D90 (90％ minimum prescription dose received by the target volume) was 36-110 Gy (median 59 Gy).After the treatment,the changes in lesion size,pain relief and complications were recorded.Results The 10 patients were followed up for 4.3-16.1 months,the median follow-up time was 9.7 months.The 2-month local control rate and the 2-month effective rate were 100％ and 58.3％,respectively.The 2-month,6-month and 12-month survival rates were 100％,66.7％ and 58.3％,respectively.The median survival time was 12.1 months.One patient (10％) died of gastrointestinal bleeding at five months after treatment,six patients (60％) died of distant metastases,three patients (30％) survived withno evidence of local recurrence.No major complications such as massive hemorrhage,intestinal infection,bone marrow suppression or other 125I seed-related complications occurred.Conclusion For the treatment of retroperitoneal lymph node metastasis due to recurrent cervical cancer after radiotherapy,CT-guided radioactive 125I seed implantation has satisfactory short-term curative effect,and this technique is safe and feasible.