Irreversible Electroporation in Patients with Pancreatic Cancer :Angel and Devil / 대한소화기암학회지

Pancreatic cancer has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancer (LAPC) is considered as unresectable because of involvement of celiac and/or mesenteric vessels. The treatment of LAPC is a challenge. Current guidelines suggest systemic therapy. However, the majority of patients will never experience conversion to surgical resection. Thus, in these patients, ablation is an alternative therapy for local control, which causes local destruction while ideally avoiding injury to surrounding healthy tissue. Irreversible electroporation (IRE) is an energy delivery system, effective in ablating tumors by inducing irreversible membrane destruction of cells. IRE demonstrated to be safe in previous studies. However, it is not free from complications, even serious. Here, we reported two cases of the IRE in LAPC patients.

Research status and progress of ablation therapy for locally advanced pancreatic cancer / 中华肝胆外科杂志

Locally advanced pancreatic cancer remains to be a disease with dismal prognosis,despite the improvements in chemotherapy or chemoradiotherapy,which was recognized as standard treatment.A heterogeneous armamentarium of locoregional ablative therapeutic options has been successfully applied for other solid organ malignancies.Recently,they were gradually applied in pancreas and commenced to show benefits.However,there are still many problems to be discussed.Here we reviewed the recent publications on the feasibility,safety and efficiency of various ablation treatments that have been applied to pancreatic cancer.

Clinical Study on Tiaogan Lipi Huaji Prescription Combined with High Intensity Focused Ultrasound for Treatment of Locally Advanced Pancreatic Cancer / 中国中医药信息杂志

Objective To investigate the effects ofTiaogan Lipi Huaji Prescription combined with high intensity focused ultrasound (HIFU) for the treatment of locally advanced pancreatic cancer.Methods Randomized, parallel controlled study was designed to select 60 patients with locally advanced pancreatic cancer, which were divided into treatment group and control group by random number table method, 30 cases in each group. The treatment group was givenTiaogan Lipi Huaji Prescription, one dose per day, twice a day, orally, 28 d as a treatment course, 6 courses in total; at the same time, HIFU was given to the treatment group, 30–60 min each time, once every other day, 2–3 times each week, and the tumor was completely covered for 2 times. The control group was given gemcitabine 1000 mg/m2, intravenous infusion, 1st, 8th d, 21–28 d for a cycle, a total of 6 cycles. The clinical benefit response, QOL-C30 score, survival status, progression-free survival (PFS), CA199 and CEA levels were observed.Results Clinical benefit rates of treatment group and control group were: the treatment group 1, 3, 6 months clinical benefit rate was 64.29%, 63.16%, and 50.00%, respectively; control group clinical benefit rate was 48.15%, 40.00%, and 44.44%, respectively, with statistical significance (P0.05). CEA levels in the treatment group were lower than those in the control group at the same time with statistical significance (P0.05). The survival time of the treatment group was (253.90±18.06)d in the control group and (246.77±17.31)d in the control group, without statistical significance (P>0.05). PFS was (136.73±16.22)d in the treatment group and (145.77±19.74)d in the control group, without statistical significance (P>0.05).ConclusionTiaogan Lipi Huaji Prescription combined with HIFU for the treatment of locally advanced pancreatic cancer has certain clinical efficacy, which can improve patients' life quality.

Irreversible electroporation for treatment of locally advanced pancreatic cancer / 中华肝胆外科杂志

Objective To evaluate the overall survival in patients with locally advanced pancreatic cancer (LAC) treated with irreversible electroporation (IRE) and chemotherapy.Methods A retrospective study on the overall survival of 30 patients with LAC treated with IRE,and 30 patients with LAC treated with chemotherapy from July 2015 to October 2016 in the PLA General Hospital was conducted.Results For the 30 patients with LAC who underwent IRE successfully,there were 21 women and 9 men.The median age was 59 (36 ～81) years.Twenty-four patients had primary pancreatic head cancer and 6 had body cancer.Twelve (40.0％) of these patients had chemotherapy after the IRE ablation.The 90-day mortality in the IRE treated patients was 3 (10.0％).For the 30 patients with LAC who were treated with chemotherapy,the 90-day mortality was 6 (20.0％).In comparison of the IRE treated patients with the chemotherapy treated patients,improvements on disease-free survival (6 months vs.4 months,P ＜ 0.05) and overall survival (11 months vs.5.6 months,P ＜ 0.05) were observed.Conclusion IRE ablation of LAC was safe and could potentially improve overall survival when compared with the standard chemotherapy treatment.

Prognostic significance of TLG on18F-FDG PET/CT imaging in patients with locally advanced pancreatic cancer undergoing radiation therapy / 中国医学装备

Objective:Total lesion glycolysis (TLG) on PET scans were calculated using custom-designed software, then we analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing radiation therapy.Methods: 33 patients with newly diagnosed LAPC who underwent 18F- FDG PET/CT scan for staging before radiation therapy were retrospectively included in this study. Patients were divided into two different groups by the median value of TLG. TLG lower than 55.3 was A group and TLG higher or equal to 55.3 was B group. TLG of tumor tissue were calculated from PET/CT images with the SUV cut-off value of 2.5. We analyzed the relationship between TLG and other clinical factors and prognosis in patients with pancreatic cancer by Kaplan-Meier method and log-rank test.Results: By Log-rank univariate analysis showed that the differences in group A and group B related significantly (r=7.765,P=0.005). And their middle survival time was 15.5 months and 8 months respectively. GTV dose of the patients in two groups and CA19-9 before treatment were also statistically different (x2=7.162, x2=10.476;P=0.05). Multivariate analysis showed that the TLG (P=0.009) were independent risk factors that prevented the long-term survival of the prognosis of patients in this group.Conclusion: The value of CA19-9 and GTV dose before treatment were the risk factors of radiotherapy for patients with locally advanced pancreatic cancer. The parameters of TLG were independent prognostic factors. TLG have a certain clinical value in predicting the prognosis of patients with pancreatic cancer, and can guide clinical diagnosis and treatment planning, and extend the lifespan of patients with pancreatic cancer.

Implantation of radioactive (125)I seeds improves the prognosis of locally advanced pancreatic cancer patients: A retrospective study / 华中科技大学学报（医学）（英德文版）

Locally advanced pancreatic cancer is associated with a very poor prognosis. This study was performed to evaluate whether patients with locally advanced pancreatic cancer benefit from (125)I seed implantation. This retrospective study included 224 patients with locally advanced pancreatic cancer, with 137 patients (61.2%) in the implantation (IP) group and 87 (38.9%) in the non-implantation (NIP) group. The survival status, complications and objective curative effects were compared between the groups. The average operative time in the IP group was significantly longer than that in the NIP group (243±51 vs. 214±77 min). The tumor response rates were 9.5% and 0 at the 2nd month after surgery in the IP and NIP groups, respectively (P<0.05). The IP group exhibited a trend toward pain relief at the 6th month after surgery. The global health status scores of the IP group were higher than those of the NIP group at the 3rd and 6th month after surgery. The median survival time in the IP group was significantly longer than that in the NIP group. In conclusion, patients with locally advanced pancreatic cancer can benefit from (125)I seed implantation in terms of local tumor control, survival time, pain relief and quality of life.

Role of Neoadjuvant Therapy for Borderline Resectable or Locally Advanced Pancreatic Cancer / 대한췌담도학회지

Surgical resection offers the only chance of cure for nonmetastatic exocrine pancreatic cancer. However, only 15 to 20 percent of patients have potentially resectable disease at diagnosis; approximately 40 percent have distant metastases, and another 30 to 40 percent have locally advanced unresectable tumors. Typically, patients with locally advanced unresectable pancreatic cancer have tumor invasion into adjacent critical structures, particularly the celiac and superior mesenteric arteries. The optimal management of these patients is controversial, and there is no internationally embraced standard approach. Therapeutic options include chemoradiotherapy or chemotherapy alone. While it is reasonable to restage and reevaluate the potential for resectability after neoadjuvant therapy, the frequency of a complete resection and long-term survival is low for patients who initially have categorically unresectable tumors. Others have disease that is categorized as "borderline resectable." While these patients are potentially resectable, the high likelihood of an incomplete resection has prompted interest in strategies to "downstage" the tumor or to increase the likelihood of a margin-negative resection prior to surgical exploration using neoadjuvant therapy. The rationale for neoadjuvant therapy is as follows. First, it is to improve the selection of patients for whom resection will not offer a survival benefit (i.e., those who rapidly progress to metastatic disease during preoperative therapy). Second, it is to increase rates of margin-negative resections, which is the major goal of surgery. Third, it is to start an early treatment of micrometastatic disease. Initial attempt at downstaging with chemotherapy, chemoradiotherapy, or a combination followed by restaging and surgical exploration in responders rather than upfront surgery is suggested.

Objective Assessment of Surgical Restaging after Concurrent Chemoradiation for Locally Advanced Pancreatic Cancer

The role of neoadjuvant chemoradiation therapy in locally advanced pancreatic cancer (LAPC) is still controversial. The aim of this study was to evaluate surgical downstaging after concurrent chemoradiation therapy (CCRT) for LAPC by measuring the objective changes after treatment. From January 2003 through July 2011, 54 patients with LAPC underwent neoadjuvant CCRT. Computed tomography findings of the tumor size, including major vessel invasion, were analyzed before and after CCRT. Among the total recruited patients, 14 had borderline resectable malignancy and another 40 were unresectable before CCRT. After CCRT, a partial response was achieved in four patients. Stable disease and further disease progression were achieved in 36 and 14 patients, respectively. Tumor size showed no significant difference before and after CCRT (3.6 +/- 1.1 vs. 3.6 +/- 1.0 cm, P = 0.61). Vessel invasion showed improvement in two patients, while 13 other patients showed further tumor progression. Thirty-nine patients with unresectable malignancy and 11 patients with borderline resectable malignancy at time of initial diagnosis remained unchanged after CCRT. Four patients with borderline pancreatic malignancy progressed to an unresectable stage, whereas one unresectable pancreatic malignancy improved to a borderline resectable stage. Only one patient with borderline resectable disease underwent operation after CCRT; however, curative resection failed due to celiac artery invasion and peritoneal seeding. The adverse events associated with CCRT were tolerable. In conclusion, preoperative CCRT in LAPC rarely leads to surgical downstaging, and it could lower resectability rates.

Induction chemotherapy with gemcitabine followed by concurrent chemoradiotherapy with capecitabine in patients with locally advanced pancreatic cancer / 中华放射医学与防护杂志

Objective To evaluate the safety and efficacy of induction chemotherapy with gemcitabine followed by concurrent chemoradiotherapywith capecitabine in patients with locally advanced pancreatic cancer (LAPC).Methods A total of 42 patients with locally advanced pancreatic cancer were enrolled.All patients received seven cycles of induction chemotherapy of gemcitabine 1 000 mg/m2,once a week.Concurrent chemoradiotherapy began 1 week after completion of induction chemotherapy.Radiotherapy was delivered with a median dose of 54 Gy (34-64 Gy) with 1.8-2.0 Gy in a fraction.The radiotherapy was combined with capecitabin at a dosage of 825 mg/m2 twice daily,5 d/week.Results Twenty patients (47.6％) were evaluated as clinical benefit response (CBR).Two cases were observed with complete remission (CR),8 with partial remission (PR),27 with stable disease (SD),and 5 with progressive disease (PD).The median overall survival was 10.1 months (range of 4-36 months).The 1-,2-year overall survival rate was 38.2％ and 18.2％,respectively.Myelosuppression was recorded in 20 patients with grades 1-2,and 5 patients with grade 3.Twenty-two patients suffered from grade 1-2 gastrointestinal toxicities,while 4 patients suffered from grade 3.Conclusions The preliminary results showed that induction chemotherapy with gemcitabine followed by concurrent chemoradiotherapy with capecitabine in patients with LAPC might achieve encouraging efficacy with better tolerance.

Prognostic Significance of Volume-Based FDG PET/CT Parameters in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation Therapy

PURPOSE: We investigated the prognostic role of volume-based parameters measured on 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scans in patients with locally advanced pancreatic cancer (LAPC) treated with chemoradiation therapy (CRT). MATERIALS AND METHODS: We enrolled 60 patients with LAPC who underwent FDG PET/CT before CRT. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary pancreatic cancers were measured on FDG PET/CT scans. Treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard models were used to determine independent prognostic factors. RESULTS: The progression-free survival (PFS), locoregional progression-free survival (LRFPS), and overall survival (OS) for this population were 6.2, 10.9, and 13.2 months, respectively. The overall treatment response rate was 16.7% at 4 weeks after CRT, and the disease control rate (DCR) was 80.0%. DCR was significantly higher in patients with low SUVmax, MTV, or TLG, and showed strong correlation with longer survival times. On univariate analysis, MTV and TLG were significant prognostic factors for PFS, LRPFS, and OS, together with pre-CRT and post-CRT CA19-9 levels. Multivariate analyses demonstrated that MTV together with the pre-CRT CA19-9 level were independent prognostic factors for PFS, LRPFS, and OS, as was TLG for LRPFS and OS. CONCLUSION: MTV and the pre-CRT CA19-9 level provided independent prognostic information in patients with LAPC treated with CRT. Volume-based PET/CT parameters may be useful in identifying which subgroup of patients would benefit from radiation therapy as a part of CRT.

A dosimetric comparison of three-dimensional conformal and intensity-modulated radiotherapy in locally advanced pancreatic cancer and a study of the clinical efficacy / 中华放射医学与防护杂志

Objective To compare the dose distribution between three-dimensional conformal radiotherapy(3D-CRT) and intensity-modulated radiotherapy (IMRT) in treating locally advanced pancreatic cancer,and report the efficacy of IMRT combined with regional chemotherapy using gemcitabine (GEM).Methods Ten patients with locally advanced pancreatic cancer were enrolled in this study.3D-CRT and IMRT plans were designed for each patient.The dose distributions of target volume and normal tissues were analyzed using the dose volume histogram (DVH).Twenty-five locally advanced pancreatic cancers patients who were treated by IMRT combined with regional chemotherapy using gemcitabine (combined group) were retrospective analyzed,as well as 25 hospitalized patients of the same period who were treated by regional chemotherapy using gemcitabine alone (chemotherapy alone group).The therapeutic efficacy and adverse events were compared between two groups.Results IMRT plans decrease the mean dose and volume of duodenum,liver,stomach,both kidney and small bowel that received highdose irradiation.The 1-,2-year survival rate of the combined group and chemotherapy alone group was 60％,28％ and 36％,12％.The median survival time of two groups was 15 and 10 months,respectively (x2 =4.16,P ＜0.05).The total response rate of the combined group and the chemotherapy alone group was 64％ and 32％,respectively (x2 =5.13,P ＜ 0.05).The upper gastrointestinal side-effect rate of the combined group was higher than that of the chemotherapy alone group(Z =-2.354,P ＜ 0.05).There was no statistic significance in hematologic toxicity,liver and renal functional damage between the two groups.Conclusions Compared with 3D-CRT plan,IMRT plan could reduce the dose of organ at risks.IMRT combined with regional chemotherapy using gemcitabine could significantly improve the survival rate of patients with locally advanced pancreatic cancer with mild adverse events.