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Survival and prognostic factors of non-small cell lung cancer patients with postoperative locoregional recurrence treated with radical radiotherapy

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Chinese Journal of Cancer 2017年第11期36卷 657-664页

作者： Li Ma Bo Qiu Jun Zhang Qi-Wen Li Bin Wang Xu-Hui Zhang Meng-Yun Qiang Zhao-Lin Chen Su-Ping Guo Hui Liu Department of Radiation Oncology Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine 651 Dongfeng Road EastGuangzhou Guangdong 510060 P. R. China

Background: locoregional recurrence remains the challenge for long-term survival of non-small cell lung cancer(NSCLC) patients after radical surgery, and curative-intent radiotherapy could be a treatment choice. This study aimed to assess the survival and prognostic factors of patients with postoperative locoregionally recurrent NSCLC treated with radical radiotherapy.Methods: We reviewed medical records of 74 NSCLC patients with postoperative locoregional recurrence who received radical radiotherapy between April 2012 and February 2016 at Sun Yat-sen University Cancer Center(Guangzhou, China). The efficacy and safety of radical radiotherapy were analyzed. The probability of survival was estimated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to identify prognostic factors.Results: Grade 3/4 adverse events included neutropenia(8 cases, 10.8%), esophagitis(7 cases, 9.5%), pneumonitis(1 case, 1.4%), and vomiting(1 case, 1.4%).The 2-year overall survival, progression-free survival, local recurrencefree survival(LRFS), and distant metastasis-free survival(DMFS) rates of all patients were 84.2,42.5,70.0, and 50.9%,respectively. Univariate and multivariate analyses showed that a higher biological effective dose(BED) of radiation was associated with longer LRFS [hazard ratios(HR)=0.317,95% confidence interval(CI) = 0.112-0.899, P = 0.016] and that wild-type epidermal growth factor receptor(EGFR) was associated with longer DMFS compared with EGFR mutation(HR = 0.383,95% CI=0.171-0.855, P = 0.019).Conclusions: Radical radiotherapy is effective and well-tolerated in NSCLC patients with postoperative locoregional recurrence. High BED is a predictor for long LRFS, and the presence of wild-type EGFR is a predictor for long DMFS.

关键词： Non-small cell lung cancer locoregional recurrence Radical radiotherapy Biological effective dose Epidermal growth factor receptor

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Role of FDG PET-CT in evaluation of locoregional nodal disease for initial staging of breast cancer

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World Journal of Clinical Oncology 2014年第5期5卷 982-989页

作者： Yiyan Liu Nuclear Medicine Service Department of RadiologyNew Jersey Medical School Newark NJ 07103 United States

Fluorodeoxyglucose positron emission tomography/computed tomography(FDG PET/CT) is not indicated or recommended in the initial staging of early breast cancer. Although it is valuable for detecting distant metastasis, providing prognostic information, identifying recurrence and evaluating response to chemotherapy, the role of FDG PET/CT in evaluating locoregional nodal status for initial staging of breast cancer has not yet been well-defined in clinical practice. FDG PET/CT has high specificity but compromised sensitivity for identifying axillary nodal disease in breast cancer. Positive axillary FDG PET/CT is a good predictor of axillary disease and correlates well with sentinel lymph node biopsy(SLNB). FDG PET/CT may help to identify patients with high axillary lymph node burden who could then move directly to axillary lymph node dissection(ALND) and would not require the additional step of SLNB. However, FDG PET/CT cannot replace SLNB or ALND due to unsatisfactory sensitivity. The spatial resolution of PET instruments precludes the detection of small nodal metastases. Although there is still disagreement regarding the management of internal mammary node(IMN) disease in breast cancer, it is known that IMN involvement is of prognostic significance, and IMN metastasis has been associated with higher rates of distant metastasis and lower overall survival rates. Limited clinical observationssuggested that FDG PET/CT has advantages over conventional modalities in detecting and uncovering occult extra-axillary especially IMN lesions with upstaging the disease and an impact on the adjuvant management.

关键词： Breast cancer Fluorodeoxyglucose positron emission tomography/computed tomography locoregional nodal disease Axillary lymph node Internal mammary lymph node Axillary lymph node dissection Sentinel lymph node biopsy

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Do Tumor Characteristics and Pre-Transplant locoregional Therapy Predict Survival after OLT in Patients with Hepatocellular Carcinoma?

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International Journal of Clinical Medicine 2013年第12期4卷 25-31页

作者： Mohamed Kohla Richard Shaw Garret Hisatak Robert Osorio Maurizio Bonacini Department of Hepatology National Liver Institute Menoufiya University Shebeen El-Kom Egypt Department of Transplantation California Pacific Medical Center San Francisco USA Research Institute California Pacific Medical Center San Francisco USA Department of Transplantation California Pacific Medical Center San Francisco USA Research Institute California Pacific Medical Center San Francisco USA

HCC prognosis after OLT is associated with criteria related to the number and size. However, the degree of differentiation and efficacy of locoregional therapies may also influence outcome. Aim: Characterize patients with and without HCC and compare outcomes according to tumor characteristics. Methods: Retrospective query of an electronic medical record of 328 patients transplanted at California Pacific Medical Center (CPMC) in 2001-2007. HCC was defined by pre-OLT listing data as well as the finding of a tumor consistent with HCC at liver explant. Milan and UCSF criteria were applied to the lesions as described by pathology upon explant examination. Results: 328 patients were evaluated, with 109 liver malignancies, 103 females (26 (25%) HCC) and 225 males (83 (37%) HCC p = 0.04). HCC patients were older (56 ± 7.2 yr) than non HCC patients (51 ± 9.2, p 0.001). The age of the donor and cold ischemia time was not different in the 2 groups. Survival was shorter in HCC (mean 984 ± 599 days) vs. non HCC (1103 ± 642) but not statistically significant (p = 0.10). Kaplan Meier survivals were superposable when comparing patients with or without malignancy and when patients with low (≤22) vs. high MELD (>22) were compared. Survival curves in patients that fulfilled Milan vs. UCSF criteria were identical. However, more patients outside Milan died of metastatic disease (5/6, 83%) vs. within Milan (6/14, 43%, p = 0.01). Cox proportional hazards regression showed that MELD, but not malignancy, differentiation or necrosis, was associated with mortality;HR = 6% (95% C.I. 1%-10%) per additional MELD point (p = 0.02). 69 pts had TACE pre-OLT, 17 had RFA ± any other modality. There was no difference in survivals in pts who received any locoregional therapy vs. those who did not (p

关键词： Tumor Characteristics locoregional Therapy Hepatolcellular Carcinoma Liver Transplantation OLT Survival

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Transarterial chemoembolization versus percutaneous microwave coagulation therapy for recurrent unresectable intrahepatic cholangiocarcinoma:Development of a prognostic nomogram

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Hepatobiliary & Pancreatic Diseases International 2020年第2期19卷 138-146页

作者： Yang Ge Seogsong Jeong Gui-Juan Luo Yi-Bin Ren Bao-Hua Zhang Yong-Jie Zhang Feng Shen Qing-Bao Cheng Cheng-Jun Sui Hong-Yang Wang Qiang Xia Lei Chen School of Public Health Shanghai Jiaotong University School of MedicineShanghai 200025China Department of Liver Surgery Renji HospitalShanghai Jiaotong University School of MedicineShanghai 200127China International Co-operation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438China National Center for Liver Cancer Shanghai 201805China Biliary Tract Department II Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China Department of Hepatobiliary Surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China Biliary Tract Department I Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China Department of Special Medical Care&Liver Transplantation Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China Department of Oncology Shanghai Cancer Center and Institutes of Biomedical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China

Background:Transarterial chemoembolization(TACE)and percutaneous microwave coagulation therapy(PMCT)are commonly used to treat intrahepatic recurrent liver cancers.However,there is no informa-tion regarding their effectiveness in patients with recurrent intrahepatic cholangiocarcinoma(ICC)after resection.Methods:A total of 275 patients with localized recurrent ICC who received either TACE(n=183)or PMCT(n=92)were studied.A propensity score matching analysis was performed to compare prognostic impact of TACE and PMCT.Prognostic factors for TACE and PMCT were identified respectively.Predictive nomograms for each TACE and PMCT were developed using the Cox independent prognostic factors and were validated in independent patient groups by receiver operating characteristic curves and area under curve values.Results:Both TACE and PMCT provided curativeness in partial patients(5-year overall survival:21.4%and 6.1%,respectively),but TACE provided better survival benefit in both overall patients(hazard ratio[HR]=0.71;95%confidence interval[CI]:0.50–0.97;P=0.034)and propensity score matching analysis(HR=0.69;95%CI:0.47–0.98;P=0.041).Independent prognostic factors for TACE were tumor size>5 cm,poor differentiation,and major resection,whereas poor differentiation,hepatitis B virus infection,cholelithiasis,and lymph node metastasis were identified for PMCT.Both predictive nomograms for TACE and PMCT were validated to be effective with area under curve values of 0.77 and 0.70,respectively.Conclusions:TACE provided better survival benefits compared to PMCT.However,there was a disparity in prognostic factors,suggesting evaluation of the two nomograms may be supportive in modality selection.Further prospective validation studies are required for the results to be applied in clinical medicine.

关键词： Bile duct cancer Biliary malignancy Cholangiocarcinoma locoregional therapy Nomogram

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The role of capecitabine as maintenance therapy in de novo metastatic nasopharyngeal carcinoma:A propensity score matching study

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Cancer Communications 2020年第1期40卷 32-42页

作者： Xue-Song Sun Sai-Lan Liu Yu-Jing Liang Qiu-Yan Chen Xiao-Yun Li Lin-Quan Tang Hai-Qiang Mai Department of Nasopharyngeal Carcinoma State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapySun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China

Background:Capecitabine was previously used as a second-line or salvage therapy for metastatic nasopharyngeal carcinoma(NPC)and has shown satisfactory curative effect as maintenance therapy in other metastatic cancers.This study aimed to explore the role of capecitabine as maintenance therapy in de novo metastatic NPC patients with different plasma Epstein-Barr virus(EBV)DNA levels before treatment.Methods:We selected de novo metastatic NPC patients treated with locoregional radiotherapy(LRRT)for this retrospective study.The propensity score matching(PSM)was applied to balance potential confounders between patients who underwent capecitabine maintenance therapy and those who did not with a ratio of 1:3.Overall survival(OS)was the primary endpoint.The association between capecitabine maintenance therapy and survival was assessed using the log-rank test and a Cox proportional hazard model.Results:Among all patients eligible for this study,64 received capecitabine maintenance therapy after LRRT.After PSM,192 patients were identified in the nonmaintenance group.In the matched cohort,patients treated with capecitabine achieved a higher 3-year OS rate compared with patients in the non-maintenance group(68.5%vs.61.8%,P=0.037).Multivariate analysis demonstrated that capecitabine maintenance therapy was an independent prognostic factor.In subgroup analysis,3-year OS rate was comparable between the maintenance and non-maintenance groups in patients with high pretreatment EBV DNA levels(˃30,000 copies/mL)(54.8%vs.45.8%,P=0.835),whereas patients with low pretreatment EBV DNA levels(≤30,000 copies/mL)could benefit from capecitabine maintenance therapy in OS(90.0%vs.68.1%,P=0.003).Conclusion:Capecitabine maintenance therapy may be superior to non-maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA≤30,000 copies/mL.groups in patients with high pretreatment EBV DNA levels(˃30,000 copies/mL)(54.8%vs.45.8%,P=0.835),whereas patients with low pretreatment EBV DNA levels(≤30,000 copies/m

关键词： capecitabine de novo Epstein-Barr virus locoregional maintenance therapy nasopharyngeal carcinoma propensity score matching radiotherapy survival

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Upfront surgery of small intestinal neuroendocrine tumors. Time to reconsider?

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World Journal of Gastroenterology 2018年第29期24卷 3201-3203页

作者： Kosmas Daskalakis Apostolos V Tsolakis Department of Surgical Sciences Uppsala University Department of Oncology and Pathology Karolinska Institute Cancer Center Karolinska Karolinska University Hospital Solna R8:04 Department of Gastrointestinal Endoscopy Karolinska University Hospital Huddinge

Small intestinal neuroendocrine tumors(SI-NETs) may demonstrate a widely variable clinical behavior but usually it is indolent. In cases with localized disease, locoregional resective surgery(LRS) is generally indicated with a curative intent. LRS of SI-NETs is also the recommended treatment when symptoms are present, regardless of the disease stage. Concerning asymptomatic patients with distant metastases, prophylactic LRS has been traditionally suggested to avoid possible future complications. Even the current European Neuroendocrine Tumor Society guidelines emphasize a possible effect of LRS in Stage IV SINETs with unresectable liver metastases. On the contrary, the 2017 National Comprehensive Cancer Network Guidelines on carcinoid tumors do not support the resection of a small, asymptomatic, relatively stable primary tumor in the presence of unresectable metastatic disease. Furthermore, a recent study revealed no survival advantage for asymptomatic patients with distant-stage disease who underwent upfront LRS. At the aforementioned paper, it was suggested that delayed surgery as needed was comparable with the upfront surgical approach in terms of postoperative morbidity and mortality, the length of the hospital stay and the rate of incisional hernia repairs but was associated with fewer reoperations for bowel obstruction. On the other hand, it is also important to note that some patients might benefit from a prophylactic surgical approach and our attention should focus on identifying this patient population.

关键词： Small intestinal neuroendocrine tumors locoregional resective surgery

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Epidemic of non-alcoholic fatty liver disease and hepatocellular carcinoma

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World Journal of Clinical Oncology 2017年第6期8卷 429-436页

作者： Adnan Said Aiman Ghufran Division of Gastroenterology and Hepatology Department of Medicine William S. Middleton VAMC University of Wisconsin School of Medicine and Public Health Gastroenterology and Hepatology Medical College of Wisconsin

Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors(diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis. Consequently NAFLD-HCC is more often diagnosed at a later stage with larger tumors and reduced opportunities for curative treatments as opposed to HCC in other causes of cirrhosis. When HCC is found at a curative stage treatments including liver transplantation, resection and loco-regional therapies are associated with good results similar to that seen in HCV-HCC. Future strategies under study include the use of chemopreventive and antioxidant agents to reduce development of cirrhosis and non-alcoholic steatohepatitis(NASH). Strategies to reverse NASH via weight loss, control of associated conditions like diabetes are key strategies in reducing the increasing incidence of NASH-HCC. Novel therapeutic agents for NASH are in trials and if successful in achieving reversal of NASH will be an important strategy in reducing NAFLD-HCC.

关键词： Non-alcoholic fatty liver disease Hepatocellular carcinoma Screening Epidemiology Pathophysiology Diagnosis Liver transplant Resection locoregional therapy Treatment

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Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation:Where do we stand?

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World Journal of Gastroenterology 2014年第18期20卷 5308-5319页

作者： Masato Fujiki Federico Aucejo Minsig Choi Richard Kim Transplant Center Cleveland ClinicClevelandOH 44195United States Department of Gastrointestinal Oncology Wayne State University/Karmonos Cancer Center DetroitMI 48202United States Department of Gastrointestinal Oncology H Lee Moffitt Cancer CenterTampaFL 33612United States

Liver transplantation(LT)for hepatocellular carcinoma(HCC)within Milan criteria is a widely accepted optimal therapy.Neo-adjuvant therapy before transplantation has been used as a bridging therapy to prevent dropout during the waiting period and as a down-staging method for the patient with intermediate HCC to qualify for liver transplantation.Transarterial chemoembolization and radiofrequency ablation are the most commonly used method for locoregional therapy.The data associated with newer modalities including drugeluting beads,radioembolization with Y90,stereotactic radiation therapy and sorafenib will be discussed as a tool for converting advanced HCC to LT candidates.The concept"ablate and wait"has gained the popularity where mandated observation period after neoadjuvant therapy allows for tumor biology to become apparent,thus has been recommended after downstaging.The role of neo-adjuvant therapy with conjunction of"ablate and wait"in living donor liver transplantation for intermediate stage HCC is also discussed in the paper.

关键词： Bridging therapy Neo-adjuvant therapy locoregional

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Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

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World Journal of Gastroenterology 2013年第34期19卷 5622-5632页

作者： Daniele Nicolini Gianluca Svegliati-Baroni Roberto Candelari Cinzia Mincarelli Alessandra Mandolesi Italo Bearzi Federico Mocchegiani Andrea Vecchi Roberto Montalti Antonio Benedetti Andrea Risaliti Marco Vivarelli Division of Hepatobiliary and Transplant Surgery Department of Gastroenterology and TransplantationPolytechnic University of Marche Division of Gastroenterology Department of Gastroenterology and TransplantationPolytechnic University of Marche Division of Interventional Radiology Department of Radiological SciencesPolytechnic University of Marche Division of Pathology Department of PathologyPolytechnic University of Marche Division of Hepatobiliary and Transplant Surgery Department of Medical and Biological SciencesUniversityof Udine

AIM:To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization(TACE)on recurrence-free survival after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and to analyze the effects of TACE on tumor histology.METHODS:We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation.Patients who received any other type of treatment such as radiofrequency tumor ablation,percutaneous ethanol ablation or who were not treated at all were excluded.All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation.Doxorubicineluting bead TACE(DEB-TACE)was performed in 22patients(38 nodules),and conventional TACE(c-TACE)in 16(25 nodules).Patients’and tumors’characteristics were retrospectively reviewed.We performed a pernodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE(conventional or DEB)and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area,including 21 nodules not reached by TACE.Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent,moderate and enhanced reaction.Uni-and multivariate analysis of risk factors for HCC-recurrence were performed.RESULTS:The number and diameter of the nodules,the time spent on the waiting list and the number of treatments were similar in the two groups.A trend towards higher appropriate response rates(necrosis≥90%)was observed in the DEB-TACE group(44.7%vs32.0%,P=0.2834).The mean percentage of necrosis in the cumulative tumor area was 58.8%±36.6%in the DEB-TACE group and 50.2%±38.1%in the c-TACE group(P=0.4856).Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group(P<0.0001,for both the parameters).The three-year recurrence-free survival was higher in DEB-TACE-treated patients than in convent

关键词： Liver transplantation Hepatocellular carcinoma Transcatheter arterial chemoembolization Doxorubicin-eluting bead Tumor histology Recurrence-free survival locoregional therapies

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Multimodal treatment of hepatocellular carcinoma on cirrhosis: An update

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World Journal of Gastroenterology 2013年第42期19卷 7316-7326页

作者： Marco Vivarelli Roberto Montalti Andrea Risaliti Hepatobiliary and Abdominal Transplantation Surgery Department of Gastroenterology and TransplantationPolytechnic University of Marche60129 AnconaItaly Department of Surgery and Transplantation University of Udine33100 UdineItaly

Hepatocellular carcinoma(HCC)is the most frequent primary liver tumor,and overall,it is one of the most frequent cancers.The association of HCC with chronic liver disease,and cirrhosis in particular,is well known,making treatment complex and challenging.The treatment of HCC must take into account the presence and stage of chronic liver disease,with the aim of preserving hepatic function that is often already impaired,the stage of HCC and the clinical condition of the patient.The different treatment options include surgical resection,transplantation,local ablation,chemoembolization,radioembolization and molecular targeted therapies;these treatments can be combined in various ways to achieve different goals.Ideally,liver transplantation is best treatment for early stage HCC on cirrhosis because it removes both the tumor and the chronic disease that produced it;however,the application of this powerful tool is limited by the scarcity of donors.Downstaging and bridging are different strategies for the management of HCC patients who will undergo liver transplantation.Several professionals,including gastroenterologists,radiologists and surgeons,are involved in the choice of the most appropriate treatment for a single case,and a multidisciplinary approach is necessary to optimize the outcome.The purpose of this review is to provide a comprehensive description of the current treatment options for patients with HCC by analyzing the advantages,disadvantages and rationale for their use.

关键词： Hepatocellular carcinoma Multimodal treatment locoregional treatments Molecular targeted therapies Liver resection Liver transplantation

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