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Pathologic tumor response to neoadjuvant therapy in borderline resectable pancreatic cancer

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Hepatobiliary & Pancreatic Diseases International 2019年第4期18卷 373-378页

作者： June S Peng Jane Wey Sricharan Chalikonda Daniela S Allende R Matthew Walsh Gareth Morris-Stiff Department of General Surgery Digestive Disease and Surgery InstituteCleveland Clinic Foundation9500 Euclid AvenueClevelandOHUSA Department of Pathology Pathology and Laboratory Medicine InstituteCleveland Clinic Foundation9500 Euclid AvenueClevelandOHUSA

Background:Previous studies have demonstrated the prognostic significance of pathologic tumor response in pancreatic adenocarcinoma following neoadjuvant therapy(NAT).The aim of this study was to determine the incidence of significant pathologic response to NAT in borderline resectable pancreatic cancer(BRPC),and association of NAT regimen and other clinico-pathologic characteristics with pathologic response.Methods:Patients with BRPC who underwent NAT and pancreatic resection between January 2012 and June 2017 were included.Pathologic response was assessed on a qualitative scale based on the College of American Pathologists grading system.Demographics and baseline characteristics,oncologic treatment,pathology,and survival outcomes were compared.Results:Seventy-one patients were included for analysis.Four patients had complete pathologic responses(tumor regression score 0),12 patients had marked responses(score 1),42 had moderate responses(score 2),and 13 had minimal responses(score 3).Patients with complete or marked responses were more likely to have received neoadjuvant gemcitabine chemoradiation(62.5%,38.1%,and 23.1%of the complete/marked,moderate,and minimal response groups,respectively;P=0.04).Of the complete/marked,moderate,and minimal response groups,margins were negative in 75.0%,78.6%,and 46.2%(P=0.16);node negative disease was observed in 87.5%,54.8%,and 15.4%(P<0.01);and median overall survival was 50.0 months,31.7 months,and 23.2 months(P=0.563).Of the four patients with pathologic complete responses,three were disease-free at 66.1,41.7 and 31.4 months,and one was deceased with metastatic liver disease at 16.9 months.Conclusions:A more pronounced pathologic tumor response to NAT in BRPC is correlated with node negative disease,but was not associated with a statistically significant survival benefit in this study.

关键词： Pancreatic cancer Borderline resectable Neoadjuvant therapy Pathologic response

The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 110-116页

作者： Ming-Liang Wang Zhang-Yan Ke Shuai Yin Chen-Hai Liu Qiang Huang Department of General Surgery Affiliated Provincial Hospital of Anhui Medical University Department of Internal Medicine The First Affiliated Hospital of Anhui Medical University

Background: The benefit of adjuvant chemotherapy for resectable cholangiocarcinoma remains unclear due to the lack of randomized control studies. This study aimed to investigate the possible benefit of postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. Data sources: Relevant research articles published before 1 st March 2018 in Pub Med, Embase and the Cochrane library databases were retrieved. Published data were extracted and analyzed by RevMan 5.3, and the results were presented as hazard ratios(HRs) [95% confidence intervals(CI)] and forest plots. Results: One prospective and eighteen retrospective studies were included, with a total number of 11,458 patients, 4696 of whom received postoperative chemotherapy. There was a significant improvement of the overall survival(OS) for patients who underwent operation + adjuvant chemotherapy compared to those who underwent operation alone(HR = 0.61; P < 0.001). Subgroup analyses show that the postoperative chemotherapy group compared with operation alone group are indicated as follows: hilar cholangiocarcinoma group(HR = 0.60; P < 0.001), intrahepatic cholangiocarcinoma group(HR = 0.60; P < 0.001), R1 resection group(HR = 0.71; P = 0.04), LN-positive diagnosis group(HR = 0.58; P < 0.001), gemcitabine-based chemotherapy group(HR = 0.42; P < 0.001), distal cholangiocarcinoma group(HR = 0.48; P = 0.17), R0 resection group(HR = 0.69; P = 0.43), and 5-flurouracil-based chemotherapy group(HR = 0.90; P = 0.66), respectively. Conclusions: Postoperative adjuvant chemotherapy can improve the OS in intrahepatic and hilar cholangiocarcinoma patients. However, distal cholangiocarcinoma patients gain no benefit from postoperative adjuvant chemotherapy. Prospective randomized trials are warranted in order to define the standard chemotherapy regimen.

关键词： resectable cholangiocarcinoma Adjuvant chemotherapy Meta-analysis

Endoscopic ultrasound-guided fiducial marker placement for neoadjuvant chemoradiation therapy for resectable pancreatic cancer

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World Journal of Gastrointestinal Oncology 2020年第7期12卷 768-781页

作者： Reiko Ashida Nobuyasu Fukutake Ryoji Takada Tatsuya Ioka Kazuyoshi Ohkawa Kazuhiro Katayama Hirofumi Akita Hidenori Takahashi Shingo Ohira Teruki Teshima Department of Cancer Survey and Gastrointestinal Oncology Osaka International Cancer InstituteOsaka 541-8567Japan Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer InstituteOsaka 541-8567Japan Department of Gastroenterological Surgery Osaka University Graduate School of MedicineOsaka 565-0871Japan Department of Surgery Osaka International Cancer InstituteOsaka 541-8567Japan Department of Radiation Oncology Osaka International Cancer InstituteOsaka 541-8567Japan

BACKGROUND Preoperative neoadjuvant chemoradiation therapy(NACRT)is applied for resectable pancreatic cancer(RPC).To maximize the efficacy of NACRT,it is essential to ensure the accurate placement of fiducial markers for image-guided radiation.However,no standard method for delivering fiducial markers has been established to date,and the nature of RPC during NACRT remains unclear.AIM To determine the feasibility,safety and benefits of endoscopic ultrasound-guided(EUS)fiducial marker placement in patients with RPC.METHODS This was a prospective case series of 29 patients(mean age,67.5 years;62.1%male)with RPC referred to our facility for NACRT.Under EUS guidance,a single gold marker was placed into the tumor using either a 19-or 22-gauge fine-needle aspiration needle.The differences in daily marker positioning were measured by comparing simulation computed tomography and treatment computed tomography.RESULTS In all 29 patients(100%)who underwent EUS fiducial marker placement,fiducials were placed successfully with only minor,self-limiting bleeding during puncture observed in 2 patients(6.9%).NACRT was subsequently administered to all patients and completed in 28/29(96.6%)cases,with one patient experiencing repeat cholangitis.Spontaneous migration of gold markers was observed in 1 patient.Twenty-four patients(82.8%)had surgery with 91.7%(22/24)R0 resection,and two patients experienced complete remission.No inflammatory changes around the marker were observed in the surgical specimen.The daily position of gold markers showed large positional changes,particularly in the superior-inferior direction.Moreover,tumor location was affected by food and fluid intake as well as bowel gas,which changes daily.CONCLUSION EUS fiducial marker placement following NACRT for RPC is feasible and safe.The RPC is mobile and is affected by not only aspiration,but also food and fluid intake and bowel condition.

关键词： Endoscopic ultrasound-guided fine-needle aspiration Interventional endoscopic ultrasound Pancreatic cancer Fiducial marker Chemoradiation resectable

Neoadjuvant treatment for resectable pancreatic adenocarcinoma

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World Journal of Clinical Oncology 2016年第1期7卷 1-8页

作者： John Wong Naveenraj L Solomon Chung-Tsen Hsueh Division of Medical Oncology and Hematology Department of Internal Medicine Loma Linda University Department of Surgery Loma Linda University

Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound(nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress.

关键词： Pancreatic cancer resectable pancreatic adenocarcinoma Neoadjuvant treatment Biomarkers Chemotherapy Surgery

Borderline resectable pancreatic cancer: Definitions and management

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World Journal of Gastroenterology 2014年第31期20卷 10740-10751页

作者： Nicole E Lopez Cristina Prendergast Andrew M Lowy Division of Surgical Oncology Department of Surgery Moores Cancer Center University of California San Diego

Pancreatic cancer is the fourth leading cause of cancer death in the United States. While surgical resection remains the only curative option, more than 80% of patients present with unresectable disease. Unfortunately, even among those who undergo resection, the reported median survival is 15-23 mo, with a 5-year survival of approximately 20%. Disappointingly, over the past several decades, despite improvements in diagnostic imaging, surgical technique and chemotherapeutic options, only modest improvements in survival have been realized. Nevertheless, it remains clear that surgical resection is a prerequisite for achieving longterm survival and cure. There is now emerging consensus that a subgroup of patients, previously considered poor candidates for resection because of the relationship of their primary tumor to surrounding vasculature, may benefit from resection, particularly when preceded by neoadjuvant therapy. This stage of disease, termed borderline resectable pancreatic cancer, has become of increasing interest and is now the focus of a multiinstitutional clinical trial. Here we outline the history, progress, current treatment recommendations, and future directions for research in borderline resectable pancreatic cancer.

关键词： Pancreatic cancer Borderline resectable pancreatic

Strategies for early detection of resectable pancreatic cancer

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World Journal of Gastroenterology 2014年第32期20卷 11230-11240页

作者： Keiichi Okanoi Yasuyuki Suzuki Department of Gastroen terological Surgery Faculty of Medicine Kagawa University

Pancreatic cancer is difficult to diagnose at an early stage and generally has a poor prognosis. Surgical resection is the only potentially curative treatment for pancreatic carcinoma. To improve the prognosis of this disease, it is essential to detect tumors at early stages, when they are resectable. The optimal approach to screening for early pancreatic neoplasia has not been established. The International Cancer of the Pancreas Screening Consortium has recently finalized several recommendations regarding the management of patients who are at an increased risk of familial pancreatic cancer. In addition, there have been notable advances in research on serum markers, tissue markers, gene signatures, and genomic targets of pancreatic cancer. To date, however, no biomarkers have been established in the clinical setting. Advancements in imaging modalities touch all aspects of the clinical management of pancreatic diseases, including the early detection of pancreatic masses, their characterization, and evaluations of tumor resectability. This article reviews strategies for screening high-risk groups, biomarkers, and current advances in imaging modalities for the early detection of resectable pancreatic cancer.

关键词： Early detection resectable Pancreatic cancer Scree

Evidence based radiation therapy for locally advanced resectable and unresectable gastric cancer

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World Journal of Gastrointestinal Oncology 2011年第9期3卷 131-136页

作者： Georgios V Koukourakis Department Radiation Oncology Anticancer Institute of Athens "Saint Savvas"

Despite the fact that gastric cancer is decreasing in incidence in the United States,it remains one of the most commonly diagnosed and most fatal cancers worldwide.In localised disease,surgery remains the cornerstone of treatment.Nevertheless,the low overall survival rates at 5 years due to locoregional and distant recurrences has led to a large debate regarding the role of radiation therapy and chemotherapy in addition to curative resection.Recent data have shown that,even with improved surgical techniques,locoregional failure rates in these patients ranged between 57% and 88%.Failures were noted in the gastric bed,regional nodes,gastric remnant,anastomosis and duodenal stump,all of which can be encompassed in a regional radiation f ield,indicating the need of further locoregional treatment.In this article,a comprehensive literature review of the reliable medical databases of PubMed and Cochrane is made and we present all available information on the role of radiation therapy in the preoperative and postoperative setting of gastric cancer.Data reported show that in locally advanced gastric cancer the addition of radiation therapy post surgery has signif icantly improved diseasefree survival as well as overall survival.Moreover,in unresectable gastric cancer,the combination of radiation therapy with chemotherapy has significantly improvedmean and overall survival rates.The role of radiation therapy in patients with resectable gastric cancer is being further evaluated in ongoing phase Ⅲ trials.

关键词： resectable gastric cancer Unresectable gastric cancer Surgery Preoperative treatment Postoperative treatment Radiation therapy

A Systematic Review of Neoadjuvant Therapy Compared to the “Resection First” Approach for Patients with Borderline resectable Pancreatic Adenocarcinoma

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Journal of Cancer Therapy 2014年第1期5卷 91-100页

作者： Paul G. Toomey Sharona Ross Shalin Shah Alexander S. Rosemurgy Florida Cancer Specialists Tampa USA The Southeastern Center for Digestive Disorders & Pancreatic Cancer Advanced Minimally Invasive & Robotic Surgery Florida Hospital Tampa Tampa USA

Background: Survival for patients with pancreatic adenocarcinoma continues to be poor. Patients with pancreatic adenocarcinoma that is deemed borderline resectable have imaging that shows disease involvement of the portal vein and/or superior mesenteric vein that is amenable to reconstruction or abutment (≤180 degrees) of the superior mesenteric artery. The best initial treatment for patients with borderline resectable pancreatic adenocarcinoma has yet to be determined. Proponents of neoadjuvant therapy purport its utility for patients with borderline resectable pancreatic adenocarcinoma with the intention of increasing the likelihood of a microscopically negative (R0) margin, but the consequences of this approach are not established. This study was undertaken to systematically review the outcomes for patients with borderline resectable pancreatic adenocarcinoma to compare neoadjuvant therapy to a “resection first” approach. Methods: A MEDLINE/PubMed search was undertaken to find all studies regarding patients who underwent neoadjuvant therapy for patients with borderline resectable pancreatic adenocarcinoma. Results: A total of 112 studies were found regarding borderline resectable pancreatic cancer. Fourteen studies contained cohorts of patients with borderline resectable pancreatic adenocarcinoma who received neoadjuvant therapy (n = 471 patients) or a resection-first approach (n = 76 patients). Resection after neoadjuvant therapy was undertaken for 233 (49%) patients. Neoadjuvant therapy followed by an R0 resection occurred for 42% of patients. For patients who underwent resection first, 71% (54/76) had an R0 margin. Conclusion: Patients with borderline resectable pancreatic adenocarcinoma were more often found to undergo neoadjuvant therapy than a “resection first” approach in the available literature. Although neoadjuvant therapy portends a high rate of R0 resections, less than half of the patients who undergo neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma undergo resection. Patient

关键词： Adenocarcinoma Borderline Cancer Chemotherapy Chemoradiation Neoadjuvant Pancreatic resectable

Conversion of Unresectable to resectable Liver Metastases from Colorectal Carcinoma Using Hepatic Arterial Chronomodulated Chemotherapy: A Case Report and Short Literature Review

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Surgical Science 2018年第10期9卷 358-366页

作者： Evgeny Y. Parnes Maria S. Sayapina Alexey A. Tryakin Mohamed Bouchahda Pasquale F. Innominato Jean-Francois Morere Francis A. Levi Rene Adam The Central Clinical Hospital of Civil Aviation Moscow Russia N.N. Blokhin Russian Oncology Research Center Moscow Russia Department of Medical Oncology Assistance Publique H&ocirc pitaux de Paris H&ocirc pital Paul Brousse Villejuif France INSERM UMRS 776 “Biological Rhythms and Cancers” Campus CNRS Villejuif France Cancer Chronotherapy Team Warwick Medical School Coventry United Kingdom Hepato-Biliary Center Assistance Publique H&ocirc pitaux de Paris H&ocirc pital Paul Brousse Villejuif France

Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progression 2 years after the beginning of treatment.

关键词： The Regional Chronomodulated Hepatic Arterial Infusion Chemotherapy Metastatic Colorectal Cancer Conversion of Unresectable to resectable Liver Metastases