Treatment patterns and survival outcomes in patients with nonmetastatic early-onset pancreatic cancer

BACKGROUND The incidence of patients with early-onset pancreatic cancer(EOPC;age≤50 years at diagnosis)is on the rise,placing a heavy burden on individuals,families,and society.The role of combination therapy including surgery,radiotherapy,and chemotherapy in non-metastatic EOPC is not well-defined.AIM To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC.METHODS A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively.Overall survival(OS),disease-free survival,and progression-free survival were estimated using the Kaplan-Meier method.Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors.RESULTS With a median follow-up time of 34.6 months,the 1-year,2-year,and 3-year OS rates for the entire cohort were 84.3%,51.5%,and 27.6%,respectively.The median OS of patients with localized disease who received surgery alone and adjuvant therapy(AT)were 21.2 months and 28.8 months,respectively(P=0.007).The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy(RCT),surgery after neoadjuvant therapy(NAT),and chemotherapy were 28.5 months,25.6 months,and 14.0 months,respectively(P=0.002).The median OS after regional recurrence were 16.0 months,13.4 months,and 8.9 months in the RCT,chemotherapy,and supportive therapy groups,respectively(P=0.035).Multivariate analysis demonstrated that carbohydrate antigen 19-9 level,pathological grade,T-stage,N-stage,and resection were independent prognostic factors for non-metastatic EOPC.CONCLUSION AT improves postoperative survival in localized patients.Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Stereotactic radiotherapy and the potential role of magnetic resonance-guided adaptive techniques for pancreatic cancer

BACKGROUND Pancreatic cancer is a malignancy with one of the poorest prognoses amongst all cancers.Patients with unresectable tumours either receive palliative care or undergo various chemoradiotherapy regimens.Conventional techniques are often associated with acute gastrointestinal toxicities,as adjacent critical structures such as the duodenum ultimately limits delivered doses.Stereotactic body radiotherapy(SBRT)is an advanced radiation technique that delivers highly ablative radiation split into several fractions,with a steep dose fall-off outside target volumes.AIM To discuss the latest data on SBRT and whether there is a role for magnetic resonance-guided techniques in multimodal management of locally advanced,unresectable pancreatic cancer.METHODS We conducted a search on multiple large databases to collate the latest records on radiotherapy techniques used to treat pancreatic cancer.Out of 1229 total records retrieved from our search,36 studies were included in this review.RESULTS Studies indicate that SBRT is associated with improved clinical efficacy and toxicity profiles compared to conventional radiotherapy techniques.Further dose escalation to the tumour with SBRT is limited by the poor soft-tissue visualisation of computed tomography imaging during radiation planning and treatment delivery.Magnetic resonance-guided techniques have been introduced to improve imaging quality,enabling treatment plan adaptation and re-optimisation before delivering each fraction.CONCLUSION Therefore,SBRT may lead to improved survival outcomes and safer toxicity profiles compared to conventional techniques,and the addition of magnetic resonance-guided techniques potentially allows dose escalation and conversion of unresectable tumours to operable cases.

Stereotactic body radiotherapy using Cyber Knife for locally advanced unresectable and metastatic pancreatic cancer

AIM: To evaluate the efficacy and toxicity of stereotactic body radiotherapy using Cyber Knife for locally advanced unresectable and metastatic pancreatic cancer.METHODS: From June 2010 to May 2014,25 patients with locally advanced unresectable and metastatic pancreatic cancer underwent stereotactic body radiotherapy.Nine patients presented with unresectable locally advanced disease and 16 had metastatic disease.Primary end-points of this study were overall survival,relief of abdominal pain,and toxicity.RESULTS: Fourteen patients were treated with a total dose of 30-36 Gy in three fractions and the remainder with 40-48 Gy in four fractions.Median follow-up was 11 mo(range: 2-25 mo).The median survival duration calculated from the time of stereotactic body radiotherapy for the entire group,the locally advanced group,and the metastatic group was 9.0 mo,13.5 mo,and 8.5 mo,respectively.Overall survival was 37% and 18% at one and two years,respectively.Abdominal pain relief was achieved within 2 wk of completing radiotherapy in the patients who received successful palliation(13 of 20 patients had significant pain).Five patients(20%) had grade 1 nausea,and one(4%) had grade 2 nausea.No acute grade 3+ toxicity was seen.CONCLUSION: Stereotactic body radiotherapy using the Cyber Knife system is a promising,noninvasive,palliative treatment with acceptable toxicity for locally advanced unresectable and metastatic pancreatic cancer.

Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer

Pancreatic cancer is highly lethal. Current research that combines radiation with targeted therapy may dramatically improve prognosis. Cancerous cells are characterized by unstable genomes and activation of DNA repair pathways, which are indicated by increased phosphorylation of numerous factors, including H2 AX, ATM, ATR, Chk1, Chk2, DNA-PKcs, Rad51, and Ku70/Ku80 heterodimers. Radiotherapy causes DNA damage. Cancer cells can be made more sensitive to the effects of radiation(radiosensitization) through inhibition of DNA repair pathways. The synergistic effects, of two or more combined non-lethal treatments, led to coadministration of chemotherapy and radiosensitization in BRCA-defective cells and patients, with promising results. ATM/Chk2 and ATR/Chk1 pathways are principal regulators of cell cycle arrest, following DNA doublestrand or single-strand breaks. DNA double-stranded breaks activate DNA-dependent protein kinase, catalytic subunit(DNA-PKcs). It forms a holoenzyme with Ku70/Ku80 heterodimers, called DNA-PK, which catalyzes the joining of nonhomologous ends. This is the primary repair pathway utilized in human cells after exposure to ionizing radiation. Radiosensitization, induced by inhibitors of ATM, ATR, Chk1, Chk2, Wee1, PP2 A, or DNA-PK, has been demonstrated in preclinical pancreatic cancer studies. Clinical trials are underway. Development of agents that inhibit DNA repair pathways to be clinically used in combination with radiotherapy is warranted for the treatment of pancreatic cancer.

Is concomitant radiotherapy necessary with gemcitabinebased chemotherapy in pancreatic cancer?

AIM: To evaluate the efficacy and safety of gemcitabine (GEM) plus radiotherapy compared with GEM alone for pancreatic cancer (PC).

Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis

AIM: To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H NMR) combined with principal components analysis (PCA) and evaluate the radiotherapeutic effect. METHODS: The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm3 , the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. 1H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiationtreated pancreatic tumor tissues were compared. RESULTS: Compared with 1H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the 1H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased. CONCLUSION: The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.

A study of transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy for local advanced pancreatic cancer

Objective: To evaluate the clinical effect of transarterial infusion chemotherapy of gemcitabine plus three dimen- sional conformal radiotherapy on patients with local advanced pancreatic cancer. Methods: Fifty-one patients with local ad- vanced pancreatic cancer from June 2002 to February 2004 were enrolled, twenty-four patients of combined group were treat- ed with transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy, while twenty-seven patients of control group were treated only with transarterial infusion chemotherapy of gemcitabine. Results: There were significant statistical differences between two groups in clinical benefit response (91.7% versus 74.1%, P < 0.01) and overall remission rate (70.8% versus 33.3%, P < 0.01). The 6-month survival rate, 12-month survival rate and 24-month survival rate of combined group were 83.3%, 62.5% and 37.5% respectively, while that of control group were 55.6%, 33.3% and 11.1% respectively. This showed significant difference between the two groups. Conclusion: Transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy may be better than single transarterial infusion chemotherapy of gemcitabine in improving survival rates and elongating survival time of patients with local advanced pancreatic cancer.

Optimal combination of radiofrequency ablation with chemoradiotherapy for locally advanced pancreatic cancer

Problems have been reported in the treatment of pancreatic cancer with radiofrequency ablation(RFA), such as the friability of the organ itself. This report presents possible solutions to such problems. Although our patient suffered from locally advanced unresectable pancreatic cancer, she remained well at 18 mo after RFA with no evidence of recurrence. To ameliorate the side effects of RFA, after a palliative bypass procedure, the subject was treated with combined radiotherapy and chemotherapy. After this regimen had been administered, a contrast-enhanced computed tomography scan confirmed that RFA is a viable approach to the treatment of pancreatic cancer as the chemoradiotherapy had resulted in marked tumor shrinkage and pancreatic fibrosis; i.e., sufficient tumor ablation was achieved without serious RFA-related complications, such as pancreatitis or pancreatic fistulae. The present case suggests that RFA combined with preceding chemoradiotherapy is safe and effective for the palliative treatment of locally advanced pancreatic cancer.

Effect of radiotherapy on angiogenesis of human pancreatic cancer transplanted tumor in nude mice

Objective: The aim of this study was to observe the effect of radiation on micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression in an transplanted tumor of human pancreatic cancer in nude mice and to explore the role of radiotherapy on pancreatic cancer angiogenesis. Methods: After vaccinated pancreatic cancer PANC-1 cells, 20 nude mice were randomly divided into radiation group and control group. Radiation group received the radiation (dose of 20 Gy) and were killed 5 days later. The MVD and VEGF expression were determined by immunohistochemistry and then compared with the control group. Results: The number of MVD in the radiation group was significantly lower than that of the control group (8.30 ± 4.55 vs. 13.60 ± 4.28, P < 0.01). The optical density (OD) of VEGF in the radiation group was higher (2.11 ± 0.54 vs. 1.32 ± 0.61, P < 0.05) compared with the control group. Conclusion: The radiotherapy can reduce the number of vessels and increase the VEGF expression of human pancreatic cancer transplanted tumor in nude mice.

Dosimetric consequences of tumor volume changes after kilovoltage cone-beam computed tomography for non-operative lung cancer during adaptive intensity-modulated radiotherapy or fractionated stereotactic radiotherapy

Objective The aim of this study was to investigate tumor volume changes with kilovoltage cone-beam computed tomography （kV-CBCT） and their dosimetric consequences for non-operative lung cancer during intensity-modulated radiotherapy （IMRT） or fractionated stereotactic radiotherapy. Methods Eighteen patients with non-operative lung cancer who received IMRT consisting of 1.8-2.2 Gy/fraction and five fractions per week or stereotactic radiotherapy with 5-8 Gy/fraction and three fractions a week were studied, kV-CBCT was performed once per week during IMRT and at every fraction during stereotactic radiotherapy. The gross tumor volume （GTV） was contoured on the kV-CBCT images, and adaptive treatment plans were created using merged kV-CBCT and primary planning computed tomogra- phy image sets. Tumor volume changes and dosimetric parameters, including the minimum dose to 95% （D95） or 1% （D1） of the planning target volume （PTV）, mean lung dose （MLD）, and volume of lung tissue that received more than 5 （Vs）, 10 （Vl0）, 20 （V20）, and 30 （V30） Gy were retrospectively analyzed. Results The average maximum change in GTV observed during IMRT or fractionated stereotactic radio- therapy was -25.85% （range, -13.09% --56.76%）. The D95 and Dr of PTV for the adaptive treatment plans in all patients were not significantly different from those for the initial or former adaptive treatment plans. In patients with tumor volume changes of 〉20% in the third or fourth week of treatment during IMRT, adap- tive treatment plans offered clinically meaningful decreases in MLD and V5, V10, V20, and V30; however, in patients with tumor volume changes of 〈 20% in the third or fourth week of treatment as well as in patients with stereotactic radiotherapy, there were no significant or clinically meaningful decreases in the dosimetric parameters. Conclusion Adaptive treatment planning for decreasing tumor volume during IMRT may be beneficial for patients who experience tumor volume changes of 〉20% in the third or fourth week of treatment.

Clinical Benefit with Intraoperative Radiotherapy Combined with Regional Chemotherapy for Advanced Pancreatic Carcinoma

Objective: To evaluate the effectiveness of intraoperative radiotherapy (IORT) in combination with regional chemotherapy in the treatment of advanced pancreatic carcinoma.Methods: 17 patients with advanced pancreatic adenocarcinoma were treated with IORT and regional chemotherapy with 5-FU, Epirubucin and Mitomycin, and 6 cases accepted external radiotherapy postoperatively.Results: 35.29% (6/17) of the patients were clinical benefit responders and 23.53% (4/17) had a partial response. The median survival time was 11 months and the 1-year survival rate was 35.29% (6/17)Conclusion: IORT in combination with regional chemotherapy had a good impact on clinical benefit without severe side effects in locally advanced pancreatic carcinoma and led to a significant prolongation of the survival time. Key words pancreatic cancer - intraoperative radiotherapy - chemotherapy

Current therapeutic strategies for advanced pancreatic cancer: A review for clinicians

Pancreatic cancer(PC) would become the second leading cause of cancer death in the near future, despite representing only 3% of new cancer diagnosis. Survival improvement will come from a better knowledge of risk factors, earlier diagnosis, better integration of locoregional and systemic therapies, as well as the development of more efficacious drugs rising from a deeper understanding of disease biology. For patients with unresectable, non-metastatic disease, combined strategies encompassing primary chemotherapy and radiation seems to be promising. In fit patients, new polychemotherapy regimens can lead to better outcomes in terms of slight but significant survival improvement associated with a positive impact on quality of life. The upfront use of these regimes can also increase the rate of radical resections in borderline resectable and locally advanced PC. Second line treatments showed to positively affect both overall survival and quality of life in fit patients affected by metastatic disease. At present, oxaliplatin-based regimens are the most extensively studied. Nonetheless, other promising drugs are currently under evaluation. Presently, in addition to surgery and conventional radiation therapy, new locoregional treatment techniques are emerging as alternative options in the multimodal approach to patients or diseases not suitable for radical surgery. As of today, in contrast with other types of cancer, targeted therapies failed to show relevant activity either alone or in combination with chemotherapy and, thus, current clinical practice does not include them. Up to now, despite the fact of extremely promising results in different tumors, also immunotherapy is not in the actual therapeutic armamentarium for PC. In the present paper, we provide a comprehensive review of the current state of the art of clinical practice and research in PC aiming to offer a guide for clinicians on the most relevant topics in the management of this disease.

Sarcopenia in pancreatic cancer–effects on surgical outcomes and chemotherapy

Sarcopenia is found in up to 65% of pancreatic cancer patients. The definition and diagnostic methods for sarcopenia have changed over the years, and the measurement of skeletal muscle mass with cross-sectional imaging has become the most popular way of assessment, although the parameters measured vary among different studies. It is still debatable that there is an association between sarcopenia and postoperative pancreatic fistula, but most studies showed a higher risk in patients with sarcopenic obesity. Long-term survival is worse in sarcopenic patients, as shown by meta-analysis. Sarcopenia is also associated with decreased survival and higher toxicity in patients receiving chemotherapy, and chemotherapy also tends to potentiate sarcopenia. Treatment for sarcopenia still remains an area for research, although oral supplements, nutritional modifications and exercise training have been shown to improve sarcopenia.

Current developments, problems and solutions in the non-surgical treatment of pancreatic cancer

Pancreatic cancer is a common malignant neoplasm of the pancreas with an increasing incidence, a low early diagnostic rate and a fairly poor prognosis. To date, the only curative therapy for pancreatic cancer is surgical resection, but only about 20% patients have this option at the time of diagnosis and the mean 5-year survival rate after resection is only 10%-25%. Therefore, developing new treatments to improve the survival rate has practical significance for patients with this disease. This review deals with a current unmet need in medical oncology: the improvement of the treatment outcome of patients with pancreatic cancer. We summarize and discuss the latest systemic chemotherapy treatments (including adjuvant, neoadjuvant and targeted agents), radiotherapy, interventional therapy and immunotherapy. Besides discussing the current developments, we outline some of the main problems, solutions and prospects in this field.

Combined radiochemotherapy in patients with locally advanced pancreatic cancer: A meta-analysis

AIM:To compare the long-term clinical efficacy of chemotherapy plus radiotherapy(CRT)with that of radiotherapy alone(RT)or chemotherapy alone(CT)for locally advanced pancreatic carcinoma(LAPC).METHODS:Using manual and computer-aided methods,we searched the data through the databases,including PubMed/EmBase/CNKI/CQVIP/China Journals Full Text Database and websites and proceedings of major annual meetings such as ASCO and CSCO.The methodological quality of the included studies was assessed using the Jadad scoring system.Both English and Chinese publications were searched.We collected data from controlled clinical trials on CRT vs RT or CT for LAPC,and conducted a meta-analysis of 15 included studies.Meta-analysis was performed using RevMan4.2Software according to the method recommended by Cochrane Collaboration.RESULTS:Fifteen eligible randomized controlled trials including a total of 1128 patients were screened.Jadad score was 2 in only one article,and 3-4 in the remaining 14 studies.The meta-analysis showed that CRT was superior in the 6-and 12-mo survivals to the RT alone group or CT alone group(P=0.0001 and P=0.02,respectively),whereas the 18-mo survival showed no significant difference(P=0.23).Subgroup analysis showed that the 6-,12-,and 18-mo survivals were not significantly different between the CRT group and CT group(P=0.07,P=0.23,and P=0.91,respectively).Notably,the CRT group had significantly better 6-,12-,and 18-mo survivals than the RT group(all P<0.01).CRT group had significantly more grade 3-4 treatmentrelated hematologic and non-hematologic toxicities than the CT group or RT group(all P<0.01).CONCLUSION:Compared with CT or RT,CRT can benefit the long-term survival of LAPC patients,although it may also increase treatment-related toxicities.

Radioactive ^125I seed implantation for locally advanced pancreatic cancer:A retrospective analysis of 50 cases

BACKGROUND Pancreatic cancer is one of the common malignant tumors of the digestive system,and radical resection is the first choice of treatment for pancreatic cancer.If patients with locally advanced pancreatic cancer cannot be treated in time and effectively,their disease often develops rapidly and their survival period is very short.AIM To evaluate the therapeutic effect of ^125I seed implantation in patients with locally advanced pancreatic cancer.METHODS The demographics and perioperative outcomes of a consecutive series of patients who underwent ^125I seed implantation to treat locally advanced pancreatic cancer between January 1,2017 and June 30,2019 were retrospectively analyzed.According to the results of preoperative computed tomography or magnetic resonance imaging,the treatment planning system was used to determine the area and number of ^125I seeds implanted.During the operation,^125I seeds were implanted into the tumor under the guidance of intraoperative ultrasound,with a spacing of 1.5 cm and a row spacing of 1.5 cm.For patients with obstructive jaundice and digestive tract obstruction,choledochojejunostomy and gastroenterostomy were performed simultaneously.After operation,the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment.RESULTS Among the 50 patients,there were 29 males and 21 females,with a mean age of 56.9±9.8 years.The main reason for the failure of radical resection was superior mesenteric artery invasion(37,74%),followed by superior mesenteric vein invasion(33,66%).Twenty-one(62%)patients underwent palliative surgery and postoperative pain relief occurred in 40(80%)patients.The estimated blood loss in operation was 107.4±115.3 mL and none of the patient received blood transfusion.The postoperative hospital stay was 7.5±4.2 d;one patient had biliary fistula and three had pancreatic fistula,all of whom recovered after conservative treatment.After operation,26 patients received chemotherapy and 24 did not.The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not(60.7%vs 35.9%,P=0.034).The mean overall survival of patients of the chemotherapy group and nonchemotherapy group was 14 and 11 mo,respectively(χ^2=3.970,P=0.046).CONCLUSION Radioactive ^125I seed implantation combined with postoperative chemotherapy can prolong the survival time,relieve pain,and improve the quality of life of patients with locally advanced pancreatic cancer.

Neoadjuvant strategies for pancreatic cancer

Pancreatic cancer(PC)is the fourth cause of cancer death in Western countries,the only chance for long term survival is an R0 surgical resection that is feasible in about 10%-20%of all cases.Five years cumulative survival is less than 5%and rises to 25%for radically resected patients.About 40%has locally advanced in PC either borderline resectable(BRPC)or unresectable locally advanced(LAPC).Since LAPC and BRPC have been recognized as a particular form of PC neoadjuvant therapy(NT)has increasingly became a valid treatment option.The aim of NT is to reach local control of disease but,also,it is recognized to convert about40%of LAPC patients to R0 resectability,thus providing a significant improvement of prognosis for responding patients.Once R0 resection is achieved,survival is comparable to that of early stage PCs treated by upfront surgery.Thus it is crucial to look for a proper patient selection.Neoadjuvant strategies are multiples and include neoadjuvant chemotherapy(nCT),and the association of nCT with radiotherapy(nCRT)given as either a combination of a radio sensitizing drug as gemcitabine or capecitabine or and concomitant irradiation or as upfront nCT followed by nRT associated to a radio sensitizing drug.This latter seem to be most promising as it may select patients who do not go on disease progression during initial treatment and seem to have a better prognosis.The clinical relevance of nCRT may be enhanced by the application of higher active protocols as FOLFIRINOX.

Comparison of efficacy between adjuvant chemotherapy and chemoradiation therapy for pancreatic cancer: AJCC stage-based approach

BACKGROUND The adjuvant treatment for patients with resected pancreatic cancer(PC)is not yet standardized.Because the prognosis differs according to the American Joint Committee on Cancer(AJCC)stage,a tailored approach to establish more aggressive treatment plans in high-risk patients is necessary.However,studies comparing the efficacy of adjuvant treatment modalities according to the AJCC stage are largely lacking.AIM To compare the efficacy of chemotherapy and chemoradiation therapy according to AJCC 8th staging system in patients with PC who underwent surgical resection.METHODS A total of 335 patients who underwent surgical resection and adjuvant treatment for PC were included.Patients were divided into three groups:Chemoradiation therapy(CRT)group,systemic chemotherapy(SCT)group and combined treatment of chemoradiation plus chemotherapy therapy(CRT-SCT)group.The primary outcomes were differences in overall survival(OS)between the three groups.The secondary outcomes were differences in recurrence-free survival,recurrence pattern and adverse events between the three groups.RESULTS Patients received CRT(n=65),SCT(n=62)and CRT-SCT(n=208).Overall median OS was 33.3 mo(95%confidence interval(CI):27.4-38.6).In patients with stage I/II,the median OS was 27.0 mo(95%CI:2.06-89.6)in the CRT group,35.8 mo(95%CI:26.9-NA)in the SCT group and 38.6 mo(95%CI:33.3-55.7)in the CRT SCT group.Among them,there was no significant difference in OS between the three groups.In 59 patients with stage III,median OS in the SCT group[19.0 mo(95%CI:12.6-NA)]and the CRT-SCT group[23.4 mo(95%CI:22.0-44.4)]was significantly longer than that in the CRT group[17.7 mo(95%CI:6.8-NA);P=0.011 and P<0.001,respectively].There were no significant differences in incidence of locoregional and distant recurrences between the three groups(P=0.158 and P=0.205,respectively).Incidences of grade 3 or higher hematologic adverse events were higher in the SCT and CRT-SCT groups than in the CRT group.CONCLUSION SCT and CRT-SCT showed significantly longer OS and recurrence-free survival than CRT in patients with AJCC stage III,while there was no significant difference in OS between the CRT,SCT and CRT-SCT groups in patients with AJCC stage I/II.Different adjuvant therapy according to AJCC stage can be applied in patients with PC.

Endoscopic ultrasound-guided fiducial marker placement in pancreatic cancer:A systematic review and meta-analysis

BACKGROUND Pancreatic cancer(PC)mortality remains high despite advances in therapy.Combination chemoradiotherapy offers modest survival benefit over monotherapy with either.Fiducial markers serve as needed landmarks for imageguided radiotherapy(IGRT).Traditionally,these markers were placed surgically or percutaneously with limitations of each.Endoscopic ultrasound-guided placement overcomes these limitations.AIM To evaluate the safety,efficacy,and feasibility of endoscopic ultrasound(EUS)-guided fiducial placement for PC undergoing IGRT.METHODS Articles were searched in MEDLINE,PubMed,and Ovid journals.Pooling was conducted by fixed and random effects models.Heterogeneity was assessed using Cochran’s Q test based upon inverse variance weights.RESULTS Initial search identified 1024 reference articles for EUS-guided fiducial placement in PC.Of these,261 relevant articles were reviewed.Data was extracted from 11 studies(n=820)meeting inclusion criteria.Pooled proportion of successful placement was 96.27%(95%CI:95.35-97.81)with fiducial migration rates low at 4.33%(95%CI:2.45-6.71).Adverse event rates remained low,with overall pooled proportion of 4.85%(95%CI:3.04-7.03).CONCLUSION EUS-guided placement of fiducial markers for IGRT of PC is safe,feasible,and efficacious.The ability to target deep structures under direct visualization while remaining minimally invasive are added benefits.Moreover,the ability to perform fine needle aspiration or celiac plexus neurolysis add value and increase patient-care efficiency.Whether EUS-guided fiducial placement improves outcomes in IGRT or offers any mortality benefits over traditional placement remains unknown and future studies are needed.

Radioactive 125I seed implantation for pancreatic cancer with unexpected liver metastasis:A preliminary experience with 26 patients

BACKGROUND Preoperative diagnosis rate of pancreatic cancer has increased year by year.The prognosis of pancreatic cancer patients with unexpected liver metastasis found by intraoperative exploration is very poor,and there is no effective and unified treatment strategy.AIM To evaluate the therapeutic effect of radioactive 125I seed implantation for pancreatic cancer patients with unexpected liver metastasis.METHODS The demographics and perioperative outcomes of patients who underwent 125I seed implantation to treat pancreatic cancer with unexpected liver metastasis between January 1,2017 and June 1,2019 were retrospectively analyzed.During the operation,125I seeds were implanted into the pancreatic tumor under the guidance of intraoperative ultrasound,with a spacing of 1.5 cm and a row spacing of 1.5 cm.For patients with obstructive jaundice and digestive tract obstruction,choledochojejunostomy and gastroenterostomy were performed simultaneously.After operation,the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment.RESULTS Preoperative imaging evaluation of all patients in this study showed that the tumor was resectable without liver metastasis.There were 26 patients in this study,including 18 males and 8 females,aged 60.5±9.7 years.The most common tumor site was the pancreatic head(17,65.4%),followed by the pancreatic neck and body(6,23.2%)and pancreatic tail(3,11.4%).Fourteen patients(53.8%)underwent palliative surgery and postoperative pain relief occurred in 22 patients(84.6%).The estimated blood loss in operation was 148.3±282.1 mL and one patient received blood transfusion.The postoperative hospital stay was 7.6±2.8 d.One patient had biliary fistula,one had pancreatic fistula,and all recovered after conservative treatment.After operation,7 patients received chemotherapy and 19 did not.The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not(68.6%vs 15.8%,P=0.012).The mean overall survival of patients in the chemotherapy group and non-chemotherapy group was 16.3 mo and 10 mo,respectively(χ2=7.083,P=0.008).CONCLUSION Radioactive 125I seed implantation combined with postoperative chemotherapy can prolong the survival time and relieve pain of pancreatic cancer patients with unexpected liver metastasis.