Clinical efficacy and safety of erlotinib combined with chemotherapy in the treatment of advanced pancreatic cancer:A meta-analysis

BACKGROUND Advanced pancreatic cancer is resistant to chemotherapeutic drugs,resulting in limited treatment efficacy and poor prognosis.Combined administration of the chemotherapeutic gemcitabine and erlotinib is considered a potential first-line treatment for advanced pancreatic cancer.However,their comparative benefits and potential risks remain unclear.AIM To assess the clinical efficacy and safety of erlotinib combined with other chemotherapy regimens for the treatment of advanced pancreatic cancer.METHODS Literature on the clinical efficacy and safety of erlotinib combined with chemotherapy for advanced pancreatic cancer was retrieved through an online search.The retrieved literature was subjected to a methodological qualitative assessment and was analyzed using the RevMan 5.3 software.Ten randomized controlled trials involving 2444 patients with advanced pancreatic cancer were included in the meta-analysis.RESULTS Compared with chemotherapeutic treatment,erlotinib combined with chemotherapy significantly prolonged the progression-free survival time of pancreatic cancer patients[hazard ratio(HR)=0.78,95%CI:0.66-0.92,P=0.003].Meanwhile,the overall survival(HR=0.99,95%CI:0.72-1.37,and P=0.95)and disease control rate(OR=0.93,95%CI:0.45-0.91,P=0.84)were not significantly favorable.In terms of safety,the erlotinib and chemotherapy combination was associated with a significantly higher risk of diarrhea(OR=3.59,95%CI:1.63-7.90,P<0.05)and rash(OR=3.63,95%CI:1.64-8.01,P<0.05)compared with single-agent chemotherapy.Moreover,the risk of vomiting(OR=1.27,95%CI:0.62-2.59,P=0.51),regurgitation/anorexia(OR=1.61,95%CI:0.25-10.31,P=0.62),and infection(OR=0.72,95%CI:0.28-1.87,P=0.50)were not significant in either group.CONCLUSION Compared with a single chemotherapeutic modality,erlotinib combined with gemcitabine can prolong progression-free survival in pancreatic cancer,but does not improve survival benefit or disease control rate,and can increase the risk of diarrhea and rash.

Systemic treatment for advanced pancreatic cancer

Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection.Despite numerous years of research and pharmaceutical development,these figures have not changed.Treatment options for advanced pancreatic cancer are still limited.This illness is typically detected at a late stage,making curative surgical resection impossible.Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy.Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities;these therapies also hold promise for pancreatic cancer.There is an urgent need for research into targeted treatment,immunotherapy,and cancer vaccines.In this review,we emphasize the founda-tional findings that have fueled the therapeutic strategy for advanced pancreatic cancer.We also address current advancements in targeted therapy,immuno-therapy,and cancer vaccines,all of which continue to improve the clinical outcome of advanced pancreatic cancer.We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.

Developments and challenges in neoadjuvant therapy for locally advanced pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC)remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries.Despite advances in cancer treatment,the 5-year survival rate for patients with PDAC remains less than 5%.In recent years,neoadjuvant therapy(NAT)has emerged as a promising treatment option for many cancer types,including locally advanced PDAC,with the potential to improve patient outcomes.To analyze the role of NAT in the setting of locally advanced PDAC over the past decade,a systematic literature search was conducted using PubMed and Web of Science.The results suggest that NAT may reduce the local mass size,promote tumor downstaging,and increase the likelihood of resection.These findings are supported by the latest evidence-based medical literature and the clinical experience of our center.Despite the potential benefits of NAT,there are still challenges that need to be addressed.One such challenge is the lack of consensus on the optimal timing and duration of NAT.Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT.In conclusion,NAT has emerged as a promising treatment option for locally advanced PDAC.However,further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease.With continued advances in cancer treatment,there is hope of improving the outcomes of patients with PDAC in the future.

Hyperthermia combined with chemotherapy vs chemotherapy in patients with advanced pancreatic cancer:A multicenter retrospective observational comparative study

BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy(CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electrohyperthermia(mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer.AIM To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer.METHODS This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer(stage Ⅲ and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128(59%) of them were treated with CHT(no-mEHT) and 89(41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT.RESULTS Median patients’ age was 67 years(range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group(20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses(45% vs 24%, P = 0.0018) and a lower number of progressions(4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions.CONCLUSION mEHT seems safe and has beneficial effects on survival and tumor response of stage Ⅲ-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.

Therapeutic Evaluation on Advanced Pancreatic Cancer Treated by Integrative Chinese and Western Medicine──Clinical Analysis of 56 Cases

Objective: In comparison with chemotherapy, to evaluate therapeutic effects on advanced pancreatic cancer treated by integrative Chinese and western medicine (ICWM) therapies. Methods: Based on the retrospective study of 56 patients with advanced pancreatic cancer, life table was applied to the analysis of patients' survival rate and Xz test to the comparison of therapeutic response between ICWM and chemotherapy groups. Results: The results showed that 1-year survival rate in the ICWM group was 55. 37%±3.24%; 2-year survival rate 34. 61%±16. 31%; 3-year survival rate 25. 96%±24. 64%; 5-year survival rate 25. 96%±24.64%; and median survival period 16. 3 months. However 1-year survival rate in the chemotherapy group was 21. 95%±27. 54% ; 2-year survival rate 7. 31%±27. 54% ; 3-year survival rate 0 % ; and median survival period 7. 5 months. The therapeutic effects between two groups were significantly different (P=0. 004). Further analysis suggested that the reduction of cancer mass in the ICWM group was more than that in chemotherapy group (P=0.049) and the improvement of advanced pancreatic cancer related-symptoms better than that of chemotherapy group (P = 0. 002). Conclusion: The ICWM comprehensive therapy is of important value in the treatment of advanced pancreatic cancer.

Implantation of Radioactive ^(125)I Seeds Improves the Prognosis of Locally Advanced Pancreatic Cancer Patients:A Retrospective Study

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.

Management of borderline and locally advanced pancreatic cancer:Where do we stand?

Many patients with pancreas cancer present with locally advanced pancreatic cancer(LAPC).The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound,axial imaging with computed tomography and magnetic resonance imaging,and diagnostic laparoscopy.The definition of resectability has historically been vague,as there is considerable debate and controversy as to the definition of LAPC.For the patient with LAPC,there is some level of involvement of the surrounding vascular structures,which include the superior mesenteric artery,celiac axis,hepatic artery,superior mesenteric vein,or portal vein.When feasible,most surgeons would recommend possible surgical resection for patients with borderline LAPC,with the goal of an R0 resection.For initially unresectable LAPC,neoadjuvant should be strongly considered.Specifically,these patients should be offered neoadjuvant therapy,and the tumor should be assessed for possible response and eventual resection.The efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad,ranging from 3%-79%.The different modalities of neoadjuvant therapy include sin-gle or multi-agent chemotherapy combined with radiation,chemotherapy alone,and chemotherapy followed by chemotherapy with radiation.This review focuses on patients with LAPC and addresses recent advances and controversies in the field.

Postoperative inflammation as a possible cause of portal vein thrombosis after irreversible electroporation for locally advanced pancreatic cancer

Portal vein thrombosis(PVT) is a rare but serious postoperative complication associated with irreversible electroporation(IRE). We report a case of postoperative PVT in a 54-year-old woman who underwent IRE for locally advanced pancreatic cancer. Drain removal and discharge of the patient from the hospital were scheduled on postoperative day(POD) 7; however, a magnetic resonance imaging scan revealed the presence of PVT. We suspected postoperative inflammation in the pancreas as the main cause of PVT. However, the patient did not undergo any medical treatment because she did not have any clinical symptoms, and she was discharged on POD 8.

Gemcitabine plus concurrent irreversible electroporation vs gemcitabine alone for locally advanced pancreatic cancer

BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after standard treatment.Irreversible electroporation(IRE)is a novel ablative strategy for LAPC.Several studies have confirmed the safety of IRE.To date,no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine(GEM)plus concurrent IRE.AIM To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC.METHODS From February 2016 to September 2017,a total of 68 LAPC patients were treated with GEM plus concurrent IRE(n=33)or GEM alone(n=35).Overall survival(OS),progression free survival(PFS),and procedure-related complications were compared between the two groups.Multivariate analyses were performed to identify any prognostic factors.RESULTS There were no treatment-related deaths.The technical success rate of IRE ablation was 100%.The GEM+IRE group had a significantly longer OS from the time of diagnosis of LAPC(19.8 mo vs 9.3 mo,P<0.0001)than the GEM alone group.The GEM+IRE group had a significantly longer PFS(8.3 mo vs 4.7 mo,P<0.0001)than the GEM alone group.Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS.CONCLUSION Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.

Arterial complication of irreversible electroporation procedure for locally advanced pancreatic cancer

Irreversible electroporation(IRE) is a non-thermal ablation technique used especially in locally advanced pancreatic carcinomas that are considered surgically unresectable.We present the first case of acute superior mesenteric artery(SMA) occlusion secondary to pancreatic IRE procedure that has not been reported before in the literature.A 66-year-old man underwent neoadjuvant chemoradiotherapy for locally advanced pancreatic ductal adenocarcinoma.IRE procedure was applied to the patient during laparotomy under general anesthesia.After finishing the procedure,an acute intestinal ischemia was detected.A conventional vascular angiography was performed and a metallic stent was successfully placed to the SMA and blood flow was maintained.It is important to be careful in such cases of tumor involvement of SMA when evaluating for IRE procedure of pancreatic tumor.

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS: We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS: Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION: Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.

A patient with unresectable advanced pancreatic cancer achieving long-term survival with Gemcitabine chemotherapy

A 68-year-old female visited a local clinic with epigastralgia. A routine laboratory test revealed jaundice and liver dysfunction. She was referred to this hospital. Abdominal computed tomography (CT) and endoscopic retrograde cholangio-pancreatography (ERCP) revealed that the density of the entire pancreas had decreased,and showed dilatation of the common bile duct (CBD) and the main pancreatic duct (MPD). Pancreatic cancer was diagnosed by cytological examination analyzing the pancreatic juice obtained by ERCP. When jaundice had decreased the tumor was observed via laparotomy. No ascites,liver metastasis,or peritoneal dissemination was observed. The entire pancreas was a hard mass,and a needle biopsy was obtained from the head,body and tail of the pancreas. These biopsies diagnosed a poorly differentiated adenocarcinoma. Hepaticojejunostomy was thus performed,and postoperative progress was good. Chemotherapy with 1000 mg/body per week of gemcitabine was administered beginning 15 d postoperatively. However,the patient suffered relatively severe side effects,and it was necessary to change the dosing schedule of gemcitabine. Abdominal CT revealed a complete response (CR) after 3 treatments. Therefore,weekly chemotherapy was stopped and was changed to monthly administration. To date,for 4 years after chemotherapy,the tumor has not reappeared.

Computed tomography-based radiomic to predict resectability in locally advanced pancreatic cancer treated with chemotherapy and radiotherapy

BACKGROUND Surgical resection after neoadjuvant treatment is the main driver for improved survival in locally advanced pancreatic cancer(LAPC).However,the diagnostic performance of computed tomography(CT)imaging to evaluate the residual tumour burden at restaging after neoadjuvant therapy is low due to the difficulty in distinguishing neoplastic tissue from fibrous scar or inflammation.In this context,radiomics has gained popularity over conventional imaging as a complementary clinical tool capable of providing additional,unprecedented information regarding the intratumor heterogeneity and the residual neoplastic tissue,potentially serving in the therapeutic decision-making process.AIM To assess the capability of radiomic features to predict surgical resection in LAPC treated with neoadjuvant chemotherapy and radiotherapy.METHODS Patients with LAPC treated with intensive chemotherapy followed by ablative radiation therapy were retrospectively reviewed.One thousand six hundred and fifty-five radiomic features were extracted from planning CT inside the gross tumour volume.Both extracted features and clinical data contribute to create and validate the predictive model of resectability status.Patients were repeatedly divided into training and validation sets.The discriminating performance of each model,obtained applying a LASSO regression analysis,was assessed with the area under the receiver operating characteristic curve(AUC).The validated model was applied to the entire dataset to obtain the most significant features.RESULTS Seventy-one patients were included in the analysis.Median age was 65 years and 57.8%of patients were male.All patients underwent induction chemotherapy followed by ablative radiotherapy,and 19(26.8%)ultimately received surgical resection.After the first step of variable selections,a predictive model of resectability was developed with a median AUC for training and validation sets of 0.862(95%CI:0.792-0.921)and 0.853(95%CI:0.706-0.960),respectively.The validated model was applied to the entire dataset and 4 features were selected to build the model with predictive performance as measured using AUC of 0.944(95%CI:0.892-0.996).CONCLUSION The present radiomic model could help predict resectability in LAPC after neoadjuvant chemotherapy and radiotherapy,potentially integrating clinical and morphological parameters in predicting surgical resection.

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study

BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy(L1)in advanced pancreatic ductal adenocarcinoma(aPDAC).FOLFOXIRI,a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil,has demonstrated efficacy and feasibility in colorectal cancer.AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions,with either FOLFOXIRI(n=165)or FOLFIRINOX(n=124)regimens.FOLFOXIRI consisted of irinotecan(165 mg/m2),oxaliplatin(85 mg/m2),leucovorin(200 mg/m2)and 5-fluorouracil(3200 mg/m2 as a 48-h continuous infusion)every 2 wk.Ninety-six pairs of patients were selected through propensity score matching,and clinical outcomes of the two treatment regimens were compared.RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts,respectively.After propensity score matching,survival rates remained similar between the two regimens in terms of overall survival(hazard ratio=1.22;P=0.219)and progression-free survival(hazard ratio=1.27;P=0.120).The objective response rate was 37.1%in the FOLFOXIRI group vs 47.8%in the FOLFIRINOX group(P=0.187).Grade 3/4 toxicities occurred in 28.7%of patients in the FOLFOXIRI cohort vs 19.5%in the FOLFIRINOX cohort(P=0.079).FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events.Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5%with both regimens.CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX.The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.

Nine-year survival of a 60-year-old woman with locally advanced pancreatic cancer under repeated open approach radiofrequency ablation:A case report

BACKGROUND Radiofrequency ablation(RFA)is gaining popularity as an additional therapy for pancreatic ductal adenocarcinoma.RFA appears to be an attractive treatment option for patients with unresectable,locally advanced and nonmetastatic pancreatic cancer.CASE SUMMARY A 60-year-old woman with 2 mo intermittent upper abdominal pains was admitted to hospital.She had undergone radical gastrectomy(Billroth II)for gastric antral cancer.Contrast-enhanced computed tomography(CECT)and abdominal ultrasound displayed a primary tumor in the neck of the pancreas.Pathological examination showed that the lesion was a pancreatic ductal adenocarcinoma.According to the results of the imaging,open approach RFA was selected to treat the primary tumor.Eight months later,CECT follow-up revealed local recurrence of the tumor,and another open RFA was performed.Although there is evidence that RFA for recurrence of other cancers such as hepatocellular carcinoma may prolong patient survival,it remains unclear whether repeat RFA for local recurrence of pancreatic cancer is feasible.The patient continued to enjoy 9 years of life following the first RFA.CONCLUSION RFA of locally advanced,nonresectable,nonmetastatic,pancreatic tumor is characterized by feasibility-based treatment giving rise to tumor reduction based on improvement of quality of life.

Experience about treatment of advanced pancreatic cancer from Professor Liu Jianfeng and a case report

Pancreatic cancer is a common malignant tumor in clinical practice.At present,the incidence of pancreatic cancer in China is increasing rapidly year by year,which seriously threatens the health and safety of nationals.Traditional Chinese medicine has advantages in the treatment of advanced pancreatic cancer.Professor Liu Jianfeng has been engaged in the treatment of chronic diseases and health care for a long time.He has improved the patient's righteousness and improved the quality of life of patients by regulating the spleen and stomach and improving sleep.This article summarizes the ideas,prescriptions and clinical cases of Professor Liu Jianfeng in the treatment of advanced pancreatic cancer,in order to provide reference for the clinical use of traditional Chinese medicine in the treatment of advanced pancreatic cancer.

Complete response in a patient of advanced pancreatic cancer treated with third-line sintilimab and anlotinib:a case report

The patient was a 63-year-old female,who was diagnosed with advanced pancreatic cancer with mediastinal lymph node and lung metastases and pleural effusion in June 2019.First-line treatment with 6 cycles of gemcitabine plus tegafur with best response of partial response.Second-line treatment was 4 cycles of nab-paclitaxel monotherapy ended up with disease progression.Third-line treatment was sintilimab with anlotinib for 10 cycles.The patient's condition has achieved clinical complete remission so far.

Systematic review of novel ablative methods in locally advanced pancreatic cancer

Unresectable locally advanced pancreatic cancer with or without metastatic disease is associated with a very poor prognosis.Current standard therapy is limited to chemotherapy or chemoradiotherapy.Few regimens have been shown to have a substantial survival advantage and novel treatment strategies are urgently needed.Thermal and laser based ablative techniques are widely used in many solid organ malignancies.Initial studies in the pancreas were associated with significant morbidity and mortality,which limited widespread adoption.Modifications to the various applications,in particular combining the techniques with high quality imaging such as computed tomography and intraoperative or endoscopic ultrasound has enabled real time treatment monitoring and significant improvements in safety.We conducted a systematic review of the litera-ture up to October 2013.Initial studies suggest that ablative therapies may confer an additional survival benefit over best supportive care but randomised studies are required to validate these findings.

High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound(HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer.

A pilot study on combination of cryosurgery and ^(125)iodine seed implantation for treatment of locally advanced pancreatic cancer

AIM: To study the therapeutic value of combination o cryosurgery and 125iodine seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, females 13), with a median age of 59 years, were enrolled in the study. Twelve patients had liver metastases. In all cases the tumors were considered unresectable after a comprehensive evaluation. Patients were treated with cryosurgery, which was performed intraoperatively or percutaneously unde guidance of ultrasound and/or computed tomography (CT), and 125iodine seed implantation, which was performed during cryosurgery or post-cryosurgery under guidance of ultrasound and/or CT. A few patients received regional celiac artery chemotherapy. RESULTS: Thirteen patients received intraoperative cryosurgery and 36 received percutaneous cryosurgery Some patients underwent repeat cryosurgery. 125Iodine seed implantation was performed during freezing procedure in 35 patients and 3-9 d after cryosurgery in 14 cases. Twenty patients, 10 of whom had hepaticmetastases received regional chemotherapy. At 3 mo after therapy, CT was repeated to estimate tumor response to therapy. Most patients showed varying degrees of tumor necrosis. Complete response (CR) of tumor was seen in 20.4% patients, partial response (PR), in 38.8%, stable disease (SD), in 30.6%, and progressive disease (PD), in 10.2%. Adverse effects associated with cryosurgery included upper abdomen pain and increased serum amylase. Acute pancreatitis was seen in 6 patients one of whom developed severe pancreatitis. All adverse effects were controlled by medical management with no poor outcome. There was no therapy-related mortality. During a median follow-up of 18 mo (range of 5-40), the median survival was 16.2 mo, with 26 patients (53.1%) surviving for 12 mo or more. Overall, the 6-, 12-, 24- and 36-mo survival rates were 94.9%, 63.1%, 22.8% and 9.5%, respectively. Eight patients had survival of 24 mo or more. The patient with the longest survival (40 mo) is still living without evidence of tumor recurrence. CONCLUSION: Cryosurgery, which is far less invasive than conventional pancreatic resection, and is associated with a low rate of adverse effects, should be the treatment of choice for patients with locally advanced pancreatic cancer. 125Iodine seed implantation can destroy the residual surviving cancer cells after cryosurgery. Hence, a combination of both modalities has a complementary effect.