bluuebunny/crossref_metadata_2025 huggingface dataset:
Current trends in the interventional treatment of hepatocellular carcinoma: A cross-sectional survey of transarterial embolization techniques.
Authors: Craig Paul , Young Shamar , Lunos Scott , Golzarian Jafar
Published: September 2018

e15627

Background: Since two randomized controlled trials demonstrated the superiority of Transarterial chemoembolization (TACE) to supportive care, it has been a mainstay of treatment for unresectable hepatocellular carcinoma (HCC). The technical aspects of the TACE procedure, including drug type, embolic agent, bead type and size, procedural endpoint and follow up are heterogeneous throughout the literature, making meaningful comparisons less impactful. The goal of this study was to determine the common technical practices in the interventional therapy of HCC over several geographical areas. Methods: An anonymous 18 question online survey was distributed via email to practicing members of the Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Chinese Society of Interventional Radiology (CSIR), Japanese Society of Interventional Radiology (JSIR), Korean Society of Interventional Radiology (KSIR), and the Society of Interventional Radiology (SIR). An estimated 15,700 surveys were distributed and 1160 responses obtained from 62 countries for a total response rate of 7.4%. Results: Excluding bead size, responses were statistically different by region (p < 0.05). Doxorubicin was more commonly used among SIR, CIRSE, and KSIR members than JSIR and CSIR members (p < 0.05). A fixed dose of cytotoxin was favored by SIR and CIRSE members, while dosing dependent on tumor-size was used by KSIR, JSIR, and CSIR members (p < 0.05). Drug eluting bead-TACE (DEB-TACE) was most popular in SIR and CIRSE, while classical TACE (cTACE) was most popular in Japan, Korea, and China (p < 0.05). For DEB-TACE procedures, the favored bead size was 100 μm – 300 μm for all groups. Procedural endpoint, type of embolic agent, and use of additives and antibiotics varied among groups (p < 0.05). CT was the most commonly used modality for follow up amongst all respondents, but MR was used more by SIR members than all other groups (p < 0.05). Conclusions: This study demonstrated that there is clear evidence that the TACE technique differs by region. Understanding and reporting the current practice trends is an important step to optimize and standardize future randomized controlled trials.
A pilot study on cisplatin-based transarterial chemoembolization combined with systemic cisplatin plus gemcitabine for advanced or metastatic intrahepatic cholangiocellular carcinoma.
Authors: Ogasawara Sadahisa , Ooka Yoshihiko , Suzuki Eiichiro , Sugiyama Harutoshi , Tawada Akinobu , Sakai Yuji , Chiba Tetsuhiro , Kanai Fumihiko , Tsuyuguchi Toshio , Yokosuka Osamu
Published: September 2018

e15629

Background: Systemic cisplatin plus gemcitabine (CisGem) is the standard treatment for patients with advanced or metastatic intrahepatic cholangiocellular carcinoma (ICC). Transarterial chemoembolization (TACE) is a treatment procedure for patients with liver cancer. This prospective study was to evaluate the safety and efficacy of cisplatin-based TACE combined with systemic CisGem in patients with ICC. Methods: Eligibility criteria were histologically or cytologically confirmed, unresectable, recurrent or metastatic mass-forming type ICC; Eastern Cooperative Oncology Group performance status 0–2; and an adequate major organ function. Patients may have had prior treatment, including surgery, but no prior CisGem therapy. Cisplatin (25 mg/m2) plus gemcitabine (1000 mg/m2) were intravenously administered on days 1 and 8 of a 21-day cycle for 12 cycles. Three sessions of TACE were scheduled—before first, fifth, and ninth cycle of CisGem. A suspension of CDDP-powder 35 mg/m2 and lipiodol was injected through tumor-feeding branch of intrahepatic lesions, and embolization of the feeding arteries was performed using gelatin sponge (UMIN000004776). Results: Of 14 patients enrolled between December 2010 and December 2013, 7 (50%) completed treatment schedule, whereas 4 (29%) and 3 (21%) discontinued due to disease progression and adverse events (one patients each due to allergic reaction, platelet count reduction, and hepatic infection), respectively. The most common severe adverse events were elevated aspartate aminotransferase (86%) and alanine aminotransferase (71%) levels; reduced neutrophil (36%), platelet (36%), and white blood cell (28%) counts; and hepatic infection (21%). Eleven patients (79%) were evaluated for objective response (RECIST version 1.1): 9 were observed to have a partial response and 2 had a stable disease. The 6-month progression-free survival rate was 64%, and median overall survival was 25.8 months. Conclusions: Cisplatin-based TACE combined with CisGem is a feasible treatment option; however, a randomized clinical trial for comparison with CisGem is required in future. Clinical trial information: UMIN000004776.
Efficacy and safety of anti-VEGF therapy in metastatic unresectable hepatocellular carcinoma: A meta-analysis.
Authors: Chintalacheruvu Lakshmi Manogna , Buddam Avanija , Kanmanthareddy Arun , Ganti Apar Kishor
Published: September 2018

e15632

Background:Conventional chemotherapy has limited role in metastatic unresectable hepatocellular carcinoma (HCC). Sorafenib is currently approved for metastatic unresectable HCC. We wanted to assess the efficacy and safety of other tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor (VEGF) receptor such as brivanib, linifanib and regorafenib in metastatic HCC. Methods: We have searched electronic databases Pubmed, Google scholar to identify published trials using brivanib, linifanib and regorafenib in HCC. The outcomes evaluated were overall survival, time to disease progression (TTDP) and adverse effects. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were then computed using the appropriate model for categorical variables. We used STATA 13.0 and Comprehensive Meta Analysis 2.0 software for all analyses. Results: We included seven randomized control studies. A combined analysis of these seven randomised control trials showed improved overall survival (OS) in VEGF-TKI group when compared to placebo HR - 0.79; (95% CI 0.62-1.00). However, there was no significant survival benefit of the newer VEGF receptor inhibitors when compared to sorafenib (HR - 1.05; 95% CI 0.95-1.17). The time to disease progression (TTDP) was significantly better in VEGF-TKI group as compared to placebo (HR - 0.61; 95% CI 0.39-0.97). However, there was no significant difference in TTDP between VEGF-TKI group and Sorafenib (HR - 0.88; 95% CI 0.66-1.16). Adverse effects were noted to be higher in VEGF-TKI group when compared to placebo (HR- 1.07; 95% CI 1.01-1.13). Conclusions: Treatment with TKI targeting VEGF receptor is associated with a significant improvement in OS and TTDP with tolerable side effect profile. Inhibiting the VEGF receptor pathway could lead to improved outcomes in HCC.
Preoperative hemoglobin-to-red cell distribution width ratio as a novel prognostic parameter in hepatocellular carcinoma after curative resection.
Authors: Lin Ze-xiao , Ruan Dan-yun , Li Yang , Wu Dong-hao , Wang Tian-tian , Lin Jin-Xiang , Wu Xiang-yuan
Published: September 2018

e15634

Background: Cumulative evidence has demonstrated that interaction between tumor and the inflammatory microenvironment plays a critical role in the development and progression of hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of hemoglobin to red cell distribution width (RDW) ratio (HRR), as a novel and simple biomarker reflecting both the host inflammatory response and nutrition status, in patients with HCC undergoing curative hepatectomy. Methods: We retrospectively analyzed 373 HCC patients treated with hepatic resection between January 2004 and December 2012. Preoperative complete blood counts were used to calculate HRR. The best cut-off for survival analysis was determined by receiver operating characteristics (ROC) curve analysis. Univariate and multivariate analyses were applied to assess HRR and other clinicopathological variables. Results: The optimal cutoff value of HRR was 1.06 with an area under the curve (AUC) of 0.591 (95% CI, 0.540-0.642, p = 0.0072). A low preoperative HRR level ( < 1.06) was significantly correlated with hypoalbuminemia, female sex, the presence of portal hypertension and elevated level of total bilirubin. After a median follow-up of 48.5 months (range, 2-148.2 months), patients with a low HRR had significantly worse 5-year overall survival (OS) (69.2% vs 83.9%, p = 0.002). However, no significant difference was observed between low and high HRR groups with respect to recurrence free survival. The HRR (p = 0.009), histological differentiation (p = 0.003), Barcelona Clinic Liver Cancer stage (p = 0.003), serum alkaline phosphatase level (p = 0.008) and serum alanine aminotransferase level (p = 0.041) were identified to be independent prognostic factors of OS by multivariate analysis. This cox model was validated by bootstrap resampling, confirming low HRR as an independent predictor of shorter OS after adjustment (p = 0.01). Conclusions: Our study demonstrates for the first time that preoperative HRR can serve as an independent prognostic maker in HCC patients after radical surgery. Incorporation of HRR into other indices may provide better prognostic stratification.
Transarterial chemoembolization with or without microwave ablation in the treatment of intermediate (BCLC B) hepatocellular carcinoma.
Authors: Shi Feng , Lian Shanshan , Wu Peihong , Shen Lujun
Published: September 2018

e15635

Background: Transarterial chemoembolization (TACE) is currently the first-line treatment for patients with intermediate (BCLC stage B) hepatocellular carcinoma (HCC). However, the prognosis of patients with intermediate HCC remains unsatisfactory, because TACE was limited by its lack of ability to achieve complete tumor necrosis. In this study, we retrospectively compare the outcome of TACE with or without microwave ablation (MWA) in the treatment of intermediate HCC. Methods: Included in this study were 140 patients with intermediate stage HCC who underwent initial TACE and were potentially amendable for MWA (the sum of the size of the largest tumor in centimeters and the number of tumors should be no more than nine; and a total tumor diameter ≤11 cm) between January 2005 and February 2015. 75 patients were treated with following MWA (TACE-MWA), and the remaining 65 patients were treated with TACE alone. Cumulative overall survival (OS) and progression-free survival (PFS) rates were compared. Results: The respective 1-, 3-, and 5-year OS rates were 80%, 30%, and 20% in the TACE group; and 96%, 69%, and 48% in the TACE-MWA group (Fig. 2). The OS was statistically significantly better in the TACE-MWA group compared with the TACE group (P < 0.001). The respective 1-, 3-, and 5-year PFS rates were 53%, 13%, and 0% in the TACE group; and 59%, 27%, and 17% in the TACE-MWA group (Fig. 3B). PFS rates between the two groups did not differ significantly (P = 0.069). Conclusions: MWA following initial TACE prolongs OS and PFS of patients with potentially amendable intermediate HCC.
Dynamically trace the prognosis of patients with hepatocellular carcinoma through constructing survival paths with time-series data.
Authors: Shen Lujun , Li Wang , Chen Chen , Shi Feng , Wu Peihong
Published: September 2018

e15636

Background: Hepatocellular carcinoma (HCC) is featured by high risk of local recurrence and intrahepatic metastasis, and always requires repeated treatment. A novel prognostic system maximally utilizes time-series data and facilitates dynamic prognosis prediction is warranted. Methods: 1341 BCLC stage B HCC patients received treatment at Sun Yat-sen University Cancer Center from Jan, 2007 to Dec, 2012 were enrolled (979 pts for derivation, 362 pts for validation). Time-series data on serum tumor markers, biochemical and hematological index, medical imaging and associated changes (CT and/or MRI) were collected. Every 3 months represented an individual time point and a total of 9 time points were defined (Table 1); data in each time interval were allocated to associated time point. To construct the survival path, the derivation cohort was sequentially divided into subgroups by one selected feature in each time point; the feature selection criteria were: 1. independent prognostic factor in Cox model; 2. most impactful based on the change of -2Log likelihood after elimination from the model. The survival path of HCC patients was further visualized and its predictive value at each time point was compared with BCLC staging system. Results: Based on the time-series data of derivation cohort, we divided the population into 13 different paths with distinct response of treatment. The survival path system showed superior prognostic value than BCLC staging system at all time points except for the no.2 time point (Table). The validation cohort showed consistent finding. Conclusions: The methodology of survival path was valuable in dynamically tracing the prognosis of HCC patients and could further facilitate treatment planning. The visualization of data by survival path could be a new tool in processing the big data of cancer in the future. [Table: see text]
Cost and morbidity of surgical management of resectable gallbladder cancer (GBC): Results from the National Inpatient Sample database.
Authors: Fountzilas Christos , Mahalingam Devalingam , Michalek Joel , Arora Sukeshi Patel
Published: September 2018

e15663

Background: GBC is the most common biliary tract cancer. Based on a retrospective, single-institution data, extended cholecystectomy (EXT) has been recommended over simple cholecystectomy (CHOL) in tumors T2 and above. Retrospective data indicate increased morbidity/mortality with removal of more than 3 segments of the liver compared to CHOL and the effect on long-term survival is unclear. Therefore, we sought to identify short-term outcomes of hospitalization, such as cost and morbidity, for surgical treatment of GBC. Methods: The National Inpatient Sample/Healthcare Cost and Utilization Project (NIS/HCUP) for years 2010, 2011, 2012 and 2013 was surveyed for GBC hospitalizations. Hospitalizations for non-surgical management of GBC were excluded. Results: We identified 5,612 cases; mean age in EXT was 66.8 years vs. 72.4 in CHOL (p<0.001). Patients insured through Medicare were less likely to have EXT (OR: 1.5, 95% CI 1.125-2.064; p=0.007). No difference based on race (OR: 1.14, 95% CI 0.854-1.519; p=0.38). Surgical/Medical morbidity is presented in Table 1. In-hospital mortality was 3.3 vs. 4.1% for EXT and CHOL, respectively (p=0.55). Mean length of stay was higher in the EXT group (9.8 vs. 8.3 days, p=0.03), cost ($32,782 vs. 22,667.3, p=0.003) and total charges ($111,714.7 vs. 81,432.9, p<0.001). Conclusions: EXT for resectable GBC is associated with higher cost of care, probably related to higher risk for surgical site infection and stump leak. Until more evidence for overall survival benefit from EXT in this rare tumor emerges, referral of patients to high-volume centers with the hepatobiliary surgery expertise is recommended. [Table: see text]
Ang-2 polymorphisms in relation to outcome in advanced HCC patients receiving sorafenib.
Authors: Marisi Giorgia , Scartozzi Mario , Faloppi Luca , Foschi Giuseppe Francesco , Lauletta Gianfranco , Valgiusti Martina , Aprile Giuseppe , Fornaro Lorenzo , Iavarone Massimo , Ercolani Giorgio , Frassineti Giovanni Luca , Amadori Dino , Casadei Gardini Andrea
Published: September 2018

e15666

Background: Angiopoietin-2 (Ang-2) is a crucial angiogenic factor. By binding to its receptor Tie2, Ang-2 cooperates with the VEGF pathway to maintain normal physiological functions. In the presence of VEGF, Ang-2 destabilizes blood vessels and promotes vascular sprouting. In cancers, Ang-2 is linked to not only angiogenesis but also invasive and metastatic phenotypes. Although sorafenib exerts no significant activity against Tie2, the predictive value of Ang-2 has been explored in 2 studies. Llovet et al conducted a large biomarker study based on SHARP study. The authors found that a high baseline plasma Ang-2 level was an independent factor for poorer OS but not for reduced sorafenib efficacy. Polymorphism analysis seems to have more advantages than protein or gene expression analysis. Gene expression analysis is performed on biological material collected at a specific time in the natural history of the disease. It is also subject to the influence of a number of laboratory biases. Conversely, polymorphism analysis can be performed at any time during the course of the disease, is not substantially influenced by laboratory biases and is less expensive. In our study we analysed the role of ANG-2 polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma treated with sorafenib. Methods: We analyzed 135 patients with hepatocellular carcinoma treated with sorafenib. Peripheral blood samples or FFPE tumor tissues were available for DNA extraction and genotyping analysis. Nine Ang-2 polymorphisms were analyzed by direct sequencing or Real Time PCR method. Results: With regard to Ang4 rs55633437 was observed that patients carrying the allele GG were associated with a better PFS and OS. The variants GG were associated with a median OS of 16.9 months vs 6.5 months of variants GT and TT (p = 0.016). The variants GT and TT were associated with a median PFS of 2.94 months vs 4.67 months of variants GG (p = 0.03). These data were confirmed by multivariate analysis Conclusions: Ang4 rs55633437 could represent prognostic markers in patients with advanced hepatocellular carcinoma treated with sorafenib.
Predictive factors of carcinoid syndrome among patients with gastrointestinal neuroendocrine tumors (GI NETs).
Authors: Cai Beilei , Broder Michael , Chang Eunice , Yan Tingjian , Metz David C.
Published: September 2018

e15690

Background: Carcinoid syndrome (CS) is associated with a significant symptom burden and deleterious impacts on quality of life. Patients may experience delays in CS diagnosis of 5 to 7 years from initial onset of symptoms, as symptoms may be mistaken for other diseases, such as irritable bowel syndrome or menopause. The current study attempts to detect factors predictive of CS prior to CS diagnosis among patients with GI NETs. Methods: Using a US administrative claims database (IMS PharMetrics) and a retrospective case-control study design, patients (≥18 years) who were newly diagnosed with GI NETs without CS (controls) were exactly matched to patients with CS (cases) based on NET diagnosis date (month and year) at a 3-to-1 ratio. For CS patients, the study index date was the first CS diagnosis date. Each control patient was assigned to have the same index month and year as the matched case patient. The most frequently observed conditions other than symptoms/diagnoses known to be associated with CS during the 1 year prior to the index date were assessed. These conditions were entered into a forward-stepwise logistic regression model to derive predictive factors. Similar methods were applied to another administrative claims database (Truven Health Analytics MarketScan) to validate these predictors. Results: In the development database 1,004 patients with GI NETs were identified, among whom 251 (25%) had CS and 753 (75%) were controls. In both databases, three factors prior to CS diagnosis were found consistently associated with higher risks for CS, including liver disorder [odds ratio (95% CI): 3.38 (2.07 - 5.51)], enlargement of lymph nodes [2.13 (1.10 - 4.11)], and abdominal mass [3.79 (1.87 - 7.69)]. Conclusions: By assessing patients with GI NET from two independent US claim databases, this study suggested that patients diagnosed with CS were 2-3 times more likely to be diagnosed with liver disorder, enlargement of lymph nodes, or abdominal mass, than those without CS during the one year prior to CS diagnosis. Future studies using patients’ medical charts are warranted to validate and interpret the findings. These findings, when validated, may aid physicians to diagnose CS patients earlier.
Prevalence of co-morbidities in elderly patients with distant stage neuroendocrine tumors.
Authors: Dasari A. , Shen Chan , Chu Yiyi , Halperin Daniel M. , Xu Ying , Zhou Shouhao , Shih Tina , Yao James C.
Published: September 2018

e15699

Background: The median age of diagnosis of neuroendocrine tumors (NETs), an indolent tumor characterized by hormone production (carcinoid syndrome, CS) when metastatic is 63 years. Patients (pts) in this age group have multiple co-morbidities. However, their prevalence among elderly pts with metastatic NET is unknown. Methods: The Surveillance, Epidemiology and End Results (SEER)-Medicare database was used to identify 2,388 elderly patients with distant stage NET (Age: < 70: 631; 70-79: 1200; > 80: 557; Race: white: 83.4%, black: 8.6%) diagnosed between 1/03 and 12/11 identified by ICD-O-3 codes with continuous Medicare Parts A and B enrollment during the one year after NET diagnosis. We examined the prevalence of common co-morbidities in the elderly population: dementia, heart conditions including ischemic heart disease (IHD), hypertension (HTN) & congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, hyperlipidemia, diabetes, arthritis, and two additional relevant comorbidities: osteoporosis (OP) and non-rheumatic tricuspid valve (TV) disorders. Pts were considered to have a condition if they had ≥ 1 inpt or ≥ 2 outpt visits indicative of the condition. We compared the prevalence in the NET group with that in a propensity score matched non-cancer group using chi-square test. Within the NET group, we also examined the association between pt characteristics and the presence of the conditions using a logistic regression model. Results: Compared to the matched non-cancer control group, NET pts were significantly (P < 0.01) more likely to have HTN (74% vs. 66%), OP (14% vs. 11%) & TV disorders (1.72% vs. 0.98%) and less likely to have dementia (7.3% vs 17.4%), IHD (23.2% vs 29%) and diabetes (30.3% vs 33.5%). CS was noted in 25.7% of the NET group and logistic regression showed that these pts with were significantly more likely to have TV disorders (AOR = 2.52, 95% CI: 1.24-5.14) and osteoporosis (AOR: 1.34, 95% CI: 1.01-1.81). Conclusions: This population-based study showed that elderly NET pts have significantly different prevalence of co-morbidities compared to non-cancer controls. The impact of these conditions on survival and therapeutic decisions is being evaluated.
Prognostic factors and effects of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.
Authors: Jin Zhaohui , Hartgers Mindy L. , Sanhueza Cristobal T. , Johnson Benny , Shubert Christopher R. , Nagorney David M. , Smoot Rory L. , Truty Mark J. , Kendrick Michael L. , Smyrk Thomas C. , Mahipal Amit
Published: September 2018

e15703

Background: The aim of this study is to identify prognostic factors and effects of adjuvant therapy for patients with ampullary adenocarcinoma who had pancreatoduodenectomy. Methods: A cohort of 123 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from January 1, 2006, through August 31, 2016 at Mayo Clinic in Rochester, MN. Only patients with ampullary carcinoma by pathology review were included and were histologically classified as pancreaticobiliary or intestinal subtypes. Median follow-up duration was 41.0 months. Patient survival and its correlation with patient and tumor variables were tested by univariate and multivariate analysis. Results: Pancreatoduodenectomy was curative-intent in 120 out of 123 patients. All 123 patients underwent radical surgery, 32 patients (26.0%) had laparoscopic pancreatoduodenectomy. Among 123 patients, there were 76 men (61.8%).Median age at diagnosis was 67.2 years. 54 patients (45%) without metastatic disease upon surgery had adjuvant therapy (35 patients had chemotherapy only while 19 patient also had radiation). Median overall survival (OS) was 91.8 months. Poor performance status at disease diagnosis (ECOG > = 1), old age ( > = 70 years), primary tumor infiltration (T), lymph node metastasis (N), and advanced disease stage (TNM) had a significant negative impact on survival (p < 0.05 by univariate analysis). Gender, diabetes at disease diagnosis, laparoscopic surgery approach, number of lymph nodes removed, number of positive lymph nodes, and tumor size did not influence survival. In multivariate analysis, ECOG score > = 1, adjuvant treatment, primary tumor infiltration (T) and lymph node metastasis (N) remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (P = 0.0388) and overall survival (p = 0.030) for patients with advanced disease (stage IIB and above). Conclusions: Poor performance status and advanced disease stage are associated with decreased survival in patients with ampullary adenocarcinoma. Patients with advanced disease should be considered for adjuvant chemotherapy.
Epigenetic regulation of cancer self-renewal differs between endocrine tumors.
Authors: Faleiro Ines , De Mello Ramon Andrade , Apolonio Joana Dias , Roberto Vania Palma , Tabori Uri , Castelo-Branco Pedro
Published: September 2018

e15717

Background: Cancer cells achieve limitless self-renewal capacity mainly through telomerase reactivation. Methylation of a specific region in the h TERT promoter, termed TERT Hypermethylated Oncologic Region (THOR), has been associated with telomerase reactivation, increased telomerase activity and patient outcome in several cancers. Methods: In this study, we assessed the methylation status of THOR using The Cancer Genome Atlas (TCGA) data on cohorts of two endocrine cancers with distinct cell proliferation rates: the highly proliferative pancreatic adenocarcinoma (n = 194 patients) and the more indolent thyroid carcinoma (n = 571 patients). Results: THOR was significantly hypermethylated in malignant cancer when compared to benign adjacent tissue in pancreatic cancer (p < 0.0001), but not in thyroid cancer. In pancreatic cancer, THOR hypermethylation could also distinguish normal tissue from early stage I disease and it associated with worst patient prognosis. Conclusions: These preliminary findings indicate that THOR can discriminate aggressive tumors from non-aggressive ones, and evidenced the diagnostic and prognostic value of THOR in pancreatic cancer.
Efficacy and tolerability of second-line nab-paclitaxel and gemcitabine (NG) after failing first-line FOLFIRINOX in patients (pts) with advanced pancreatic cancer (APC): A single-institution experience.
Authors: Zhang Hanbo , Kellett Curtis , Lambert Pascal J , Kim Christina
Published: September 2018

e15723

Background: APC is incurable and has a poor prognosis. First line chemotherapy options include 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) or NG. However, the optimal second-line regimen is unclear. In pts who progress on FOLFIRINOX and maintain a good performance status, NG may be a reasonable second line option. As such, we sought to: 1) describe the clinical and pathologic features of pts who received second line NG compared to pts who received second line gemcitabine (GEM) or best supportive care (BSC); 2) Evaluate the toxicity profile of NG in the second line setting; 3) determine whether a survival benefit exists with second line NG. Methods: Pts ≥18 diagnosed with APC from 2012-2016 and treated with palliative chemotherapy at CancerCare Manitoba (CCMB) were identified from the Manitoba Cancer Registry. CCMB pharmacy records identified pts who received FOLFIRINOX followed by second line NG, GEM or BSC. A retrospective analysis was performed to identify pts and treatment characteristics, toxicity, dose reductions, dose delays and survival. Results: 146 pts received first line FOLFIRINOX. Of those who progressed and were offered second line therapy, 30 (50%) received NG, 8 (16%) received GEM and 22 (37%) chose BSC. Median age at diagnosis was 61 (35-84), 47% were female, 73% had metastatic disease and 63% had primaries in the head of pancreas. Grade 3 and 4 neutropenia was more common with NG compared to GEM (27% vs. 6.7%). There were more dose reductions and dose delays with NG compared to GEM (76.7% vs. 25% and 63.3% vs. 12.5% respectively). The median progression free survival was 3.61 months in the NG group, compared with 2.51 months in the GEM group (hazard ratio 2.48; 95% CI 1.08-5.65; P = 0.03). The median OS was 5.69 months in the NG group compared to 3.82 months the GEM group (hazard ratio 2.611; 95% CI, 1.11-6.38). Conclusions: In a select group of pts with APC who progress after first line FOLFIRINOX, there is a role for second line NG. Although many pts required dose reductions and delays, second line NG was associated with a survival benefit compared to GEM, with manageable toxicity.
Radioembolization with yttrium-90 resin microspheres for liver metastases of pancreatic adenocarcinoma: A retrospective multicenter analysis.
Authors: Kim Alexander Y. , Frantz Shelby , Akhter Nabeel , Zhang Jian
Published: September 2018

e15745

Background: Patients with chemotherapy-treated metastatic pancreatic cancer typically survive for 7 to 11 months. Liver metastases from the pancreas are common and can reduce survival. Radioembolization of these metastases with Y-90 resin microspheres (Y-90 resin) may reduce tumor burden and improve prognosis, but data are limited. We report early data from a multicenter database of patients with pancreatic adenocarcinoma treated with Y-90 resin. Methods: Retrospective patient, treatment, and outcome data were entered by each site (Georgetown, U Maryland). Outcomes included overall survival (OS, determined with Kaplan-Meier analyses), response rate (RECIST), and adverse events (AEs; CTCAE v4.0). Results: Data from the first 24 patients (79% male, mean age 63 y [range 51-77 y]) were analyzed. ECOG status was 0 (n = 10), 1 (n = 13), and 2 (n = 1). Median (IQR) time from diagnosis to Y-90 resin was 10.2 (6.1) mo. Nine patients had extrahepatic disease. Median (IQR) dose delivered to the right (n = 14), left (n = 2), or whole (n = 8) liver was 1.36 (0.42) GBq. Y-90 resin was given concurrently with first-line chemotherapy in 12/21 patients (57%), with a minimum of 4 mo between the onset of chemotherapy and Y-90 resin treatment. Median OS was 6.0 mo (95% CI: 3.9, 12.5) from Y-90 resin and 16.7 mo (95% CI: 13.3, 26.1) from diagnosis. Five patients experienced a partial response. Most AEs were grade 1 or 2. Three patients had grade 3 AEs (abdominal distension or pain, fatigue, ascites, odynophagia, oral sores, biliary duct dilation), and 4 had grade 3 laboratory values (white blood cells, bilirubin, alkaline phosphatase, albumin). Two patients experienced grade 4 AEs, 1 with peripheral neuropathy and 1 with elevated ALT & AST suggesting post-radioembolization hepatitis. Conclusions: Overall, Y-90 resin was safe, with few serious AEs. Survival in this retrospective study was promising, given the generally poor prognosis for pancreatic adenocarcinoma; however, further investigation is needed.
The efficacy of addition of chemoradiotherapy to achieve resectability in locally-advanced pancreatic cancer remaining unresectable after neoadjuvant chemotherapy.
Authors: Mukherjee Sarbajit , Weir Joshua , Morton Jordan , Herman Terence S. , Khalid Bilal , Postier Russell , Hatoum Hassan
Published: September 2018

e15761

Background: Although the efficacy of neoadjuvant chemotherapy (NACT) in achieving resectability in locally advanced pancreatic cancer (LAPC) has been 20-31%, many cases remain unresectable. The aim of this study is to evaluate the efficacy of adding chemo radiotherapy (CRT) to achieve resectability in LAPC that remained unresectable after NACT. Methods: Between January 2008 and December 2016, 38 patients with LAPC (borderline resectable or unresectable pancreatic cancer, BRPC or URPC) received NACT and remained unresectable; subsequently, all patients received CRT in an attempt to achieve resectability with curative-intent. The primary objective of this retrospective single institution study is to assess resection rate (RR) in these patients. The secondary objective is to assess overall survival (OS). Results: A total of 38 patients (22 male, 16 female) who were identified as BRPC (50%) or URPC (50%) at presentation as defined by multidisciplinary tumor board using pancreatic protocol CT scan received NACT and remained unresectable. The median age was 64 (56-70.5) years. The primary site was head of pancreas in 66% versus other sites in 34% . The T-stage distribution was T1 (2.6%), T2 (2.6%), T3 (34.2%) and T4 (60.6%). N0 and N1 were 63.1% and 36.9% respectively. The types of NACT included FOFIRINOX (39.5%), Gemcitabine-based (58%) and unknown (2.5%). The median number of NACT cycles was 4 (2.25-4). All patients received subsequent CRT. Only the primary tumor was targeted with a median dose of 5040 (4950-5400) cGy and a median number of fractions 18(18-28). Chemo used concurrently with radiation was 5-FU (52.5%), Xeloda (39.5%), Gemcitabine (5.5%) and unknown (2.5%). Of note, 36.8 % patients achieved resectablity (14/38). The R0 and R1 resections were 11 (28.9%) and 3 (7.9%) respectively. 52.6% patients received adjuvant chemotherapy. The OS was 17 (6-24) months in the R0 group versus 8 (7-9) months in the R1 group. For the whole group, median OS was 11.5 (7-18.25) months. Conclusions: The addition of CRT to NACT in LAPC may improve resectability leading to an OS that approximates the OS in those patients who had upfront resectable disease.
A comparison of percutaneous and endoscopic-guided celiac plexus block/neurolysis in pancreatic cancer patients.
Authors: Kambhampati Swetha , Sugar Elizabeth A. , Herman Joseph M. , Erdek Michael A. , Shin Eun Ji , Laheru Daniel A.
Published: September 2018

e15767

Background: Celiac plexus block (CPB) and celiac plexus neurolysis (CPN) are options for pain control in pancreatic cancer. Conventionally they are performed percutaneously (PC) with fluoroscopic or CT guidance. However endoscopic ultrasound (EUS) guidance is being increasingly used. The aim of this retrospective study is to compare PC-guided and EUS-guided CPB/CPN for pain control. Methods: Our retrospective cohort study included pancreatic cancer patients who underwent CPN/CPB for pain control from 2008 to 2015 at Johns Hopkins. Patients were assessed immediately post-procedure and at 1 month. Patients were selected using CPT and ICD diagnosis code guided searches of the EHR. Pain intensity was assessed using a Numeric Rating Scale (NRS). A response was defined as a decrease in NRS scores by = > 3 points. The validated FACT-Hep score was used to assess quality of life (QOL). Opiate usage was converted into morphine dosage equivalents. Wilcox rank-sum and Fisher’s exact test were used to compare the EUS and PC cohorts. Results: Of 107 patients, 46 (43%) had EUS-CPN, 57 (53%) PC-CPN, and 4 (4%) PC-CPB. 10 patients had procedural complications (7% EUS and 11% PC, p = 0.51) with the most common being chronic diarrhea. The baseline median NRS score was 7 with significantly higher scores for those receiving EUS compared to PC (9 vs 7, p < 0.001). Immediately post-procedure, more PC patients (87%) had a response when compared to EUS patients (72%), although it did not reach statistical significance (p = 0.08). By one month, there was no difference in response rates. (43% CPN vs 34% EUS, p = 0.42) FACT-Hep score declined significantly in all patients with a median drop of 8 points at 1 month and no difference between PC and EUS (9 vs 8, p = 0.46). There was no difference in opiate usage at 1 month (88% PC vs 93% EUS, p = 0.51). Conclusions: Both EUS and PC-guided CPN were effective at reducing post-procedural pain in pancreatic cancer patients but their effectiveness waned by 1 month. EUS did have slightly fewer complications although PC did have slightly higher rates of response post-procedurally. QoL declined and opiate usage was unchanged in both groups. Both procedures had temporary efficacy and need further evaluation.
PANOVA: A phase II study of TTFields (150 kHz) concomitant with standard chemotherapy for front-line therapy of advanced pancreatic adenocarcinoma—Updated efficacy results.
Authors: Benavides Manuel , Guillen Carmen , Rivera Fernando , Gallego Javier , Lopez-Martin Jose A. , Küng Marc
Published: September 2018

e15790

Background: TTFields are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. PANOVA was the first trial testing TTFields in pancreatic cancer patients. Results from the first arm of the study, testing TTFields in combination with gemcitabine, have demonstrated superiority in efficacy compared to historical controls (Rivera F. et al, J Clin Oncol 34, 2016 (suppl 4S; abstr 269). Methods: Twenty advanced pancreatic cancer patients were enrolled in the second arm of PANOVA and treated with TTFields in combination with gemcitabine concomitant to nab-paclitaxel. All patients had unresectable tumors, an ECOG performance score of 0-1 and no prior therapy. The primary endpoint was the incidence and severity of adverse events. Results: The median age was 68.2 (range – 58-81) and most patients (65%) had an ECOG score of 1. Twelve patients (60%) had distant metastases. Ten patients (50%) had serious AEs during the study period. Eleven patients (55%) had treatment-related skin toxicity, of which 5 had grade 3 toxicity. No TTFields-related serious AEs were reported. The median PFS was 12.7 months (95% CI 5.4, NA): 9.3 months in patients with metastatic disease, and not reached in locally-advanced patients. PFS rate at 6 months was 65%: 50% in metastatic disease and 87.5% in locally advanced patients. Of the evaluable tumors, 40% had partial response and another 47% stable disease. The median OS was not reached, and the 1-year survival rate was 72% (62.5% in metastatic disease and 87.5% in locally advanced disease). Conclusions: TTFields concomitant to gemcitabine and nab-paclitaxel are safe for advanced pancreatic cancer patients, with promising clinical outcome which doubled historical data. A phase III trial is planned, testing the efficacy of TTFields combined with gemcitabine and nab-paclitaxel in locally-advanced pancreatic cancer patients. Clinical trial information: NCT01971281.
Effect of GemRIS (gemcitabine-releasing intravesical system, TAR-200) on antitumor activity in muscle-invasive bladder cancer (MIBC).
Authors: Daneshmand Siamak , Pohar Kamal S. , Steinberg Gary D. , Aron Manju , Cutie Christopher
Published: September 2018

e16000

Background: Efficacy of current intravesical cytotoxic therapy for bladder cancer is limited by suboptimal dwell times and dose, and may result in local toxicities. GemRIS™ is a novel drug-device combination product that continuously delivers gemcitabine into the bladder over 7 days. Preclinical models demonstrated that GemRIS was well tolerated and resulted in no appreciable systemic exposure. Methods: This Phase 1b study evaluating the safety and tolerability of 2 GemRIS system deployments of 7 days each, separated by a 14-day rest period, in patients with confirmed MIBC scheduled for radical cystectomy (RC). A secondary endpoint included pathologic tumor response. Patients were required to have grossly visible tumor measuring > / = 3 cm in size at study entry. Pharmacokinetic (PK) analyses were conducted in blood and urine. Response to GemRIS was assessed grossly and by histopathologic analysis. Results: 10 subjects were dosed with GemRIS and underwent RC. There were no treatment-related SAEs or discontinuations; no subject requested GemRIS removal. There was no evidence of treatment-related cytopenias and no events that resulted in a delay in RC. PK analyses have demonstrated measurable levels of gemcitabine in the urine with no detectable levels in plasma. Eighty percent (8/10) of patients experienced a reduction in exophytic tumor volume; 40% exhibited complete ablation of muscle invasive disease within this short 4-week course of therapy. Conclusions: GemRIS has demonstrated encouraging preliminary efficacy and safety. Further evaluation of GemRIS in MIBC is warranted. Clinical trial information: NCT02722538. [Table: see text]
Diagnostic value of DNA aneuploidy for urothelial carcinoma.
Authors: Zhang Pei , Liang Chao Zhao , Li Jun
Published: September 2018

e16007

Background: The incidence and mortality of urologic cancer are increasing in China and worldwide. Early diagnosis is the key to improve survival. DNA-Image-Cytometry (DNA-ICM) is to assist in the early microscopical diagnosis and grading of various types of tumors, measuring the DNA-contents of their cells. This study investigates the role of DNA aneuploidy in improving diagnostic sensitivity and specificity for urothelial carcinoma. Methods: 274 voided urine samples (204 cases from patients with urothelial carcinomas and 70 cases from patients with benign urinary system diseases) were analyzed with DNA-ICM and liquid-based cytology (LBC) .Fresh urine samples were collected in the morning of the analysis. Sedimented cell-preparations were obtained through centrifugation (cytospins) for DNA-ICM. The sensitivity and specificity of DNA ICM and LBC were calculated by comparing with the pathology in cells with moderate and severe dysplasia. Results: Sensitivity of DNA-ICM was 70.3% which was much higher than that of liquid-based cytology (27.2%)(P < 0.01). Specificity of DNA-ICM was 100% while specificity of LBC was 98.6%. The sensitivity of DNA-ICM in upper urinary tract urothelial cell carcinoma(UTCUs) were 68.75%, lower than 75.00% in bladder urothelial cell carcinomas, there was no significant differences between them(P > 0.01). Conclusions: DNA single cell cytometry represents a highly relevant tool in the objective identification of urothelial carcinoma with a sufficient sensitivity and specificity. Enhancing its extended use as an adjuvant strategy for the early screening of the urothelial carcinoma during routine analyses is benefical. DNA-ICM is an effective screening method for urothelial cancer. Its use to monitor the treatment should be further validated in larger series.
Patients treated with bladder preserving trimodality chemoradiation therapy (BPTMCRT) off-trial compared to those on trials.
Authors: Ahamad Anesa Waheda , Martinez Alvaro , Salenius Sharon , Ross Rudi , Fernandez Eduardo
Published: September 2018

e16014

Background: We assessed characteristics and outcome of patients treated with radiotherapy for muscle-invasive bladder cancer off-trial at forty-four community-based radiotherapy centers in the United States compared to those on clinical trials. Methods: We retrospectively reviewed 155 patients who had been treated from August 2010 to June 2014. Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. Results were compared to a pooled analysis of six RTOG protocols. Results: Characteristics were significantly inferior versus those on RTOG studies: lower rate of complete transurethral resection of bladder tumor: 36.8% versus 70.7% (p<0.0001), poorer performance status (PS): 36.8% were 0 to 1 versus 100% (p<0.0001), higher median age: 79 years versus 66 (p<0.0001), more medically inoperable: (51.0%) versus 0% in RTOG (p<0.001). Forty-seven percent had refused surgery. Fewer patients underwent concurrent chemotherapy: 56.1% versus 100% (p<0.0001). Median radiotherapy dose was similar: 64.8 Gy. At median follow-up of 12.6 months (range, 3.1-49.2), 36-month OS was 51.3% for those who refused surgery versus 24.5% for medically inoperable (p=0.009); 36-month OS was 58.1% post complete TURBT versus 29.8% if incomplete (p=0.07); 18-month PFS was 74.9% for PS 0-1 versus 36.3% for >1 (p=0.04). PS >1 patients were deceased or censored by 24 months. The 36-month OS was 54.3% with chemoradiation therapy (CRT) versus 17.2% without chemotherapy (p=0.03). Among CRT patients, the 36-month OS was 38.9% for medically inoperable versus 66.3% for those who refused surgery (p=0.04), similar to the pooled analysis of prospective RTOG protocols. Conclusions: The 66.3% 36-month OS for patients who refused surgery and received CRT suggests that it is appropriate to offer BPTMCRT to these patients in free standing centers. However, we may not be able to translate clinical trial protocols to many patients in this setting due to their poor functional reserve. More treatment options are needed for these patients given the aging population.
Differences in survival between symptomatic versus asymptomatic recurrence following cystectomy for bladder cancer.
Authors: Osterman Chelsea K , Alanzi Jaber , Kaufman Elizabeth L , Narayan Vivek , Boursi Ben , Cambareri Christine , Malkowicz S. Bruce , Mamtani Ronac
Published: September 2018

e16021

Background: The benefit of surveillance after curative treatment in bladder cancer is controversial, but might be justified if early detection of asymptomatic recurrence improves survival. Prior studies demonstrating a benefit of surveillance may have been impacted by lead-time bias, which is the overestimation of survival duration due to earlier detection of disease. To avoid this bias, we examined time-dependent differences in survival with symptomatic vs. asymptomatic diagnosis of recurrence after cystectomy. Methods: We conducted a retrospective cohort study among 463 cystectomy patients between 1987 and 2011 at the University of Pennsylvania. Patients were followed by standardized protocol and classified by mode of recurrence detection (asymptomatic or symptomatic). Primary outcome was all-cause mortality. To reduce lead-time bias, we used cox regression models with varying cohort-entry times to assess the impact of mode of recurrence on survival from both time of cystectomy (Model 1) and time of recurrence (Model 2), adjusted for time to recurrence. Results: 197 patients (42.5%) recurred; 71 were asymptomatic (36.0%), 107 were symptomatic (54.3%), and 19 (9.6%) were unknown. In all models, relative to asymptomatic patients, patients with symptomatic recurrence had significantly increased risk of death (Model 1 HR 1.74, 95% CI 1.13-2.68, Model 2 HR 1.98, 95% CI 1.27-3.10) and had lower 1 year overall survival (30.43% vs. 55.66%). Group differences in median survival (246 days) were greater than the estimated lead-time (10 days). Conclusions: Symptomatic recurrence is associated with worse outcomes than asymptomatic recurrence, even after lead-time bias adjustment. These data support consensus guidelines for intensive surveillance post-cystectomy. Similar methods to account for lead-time bias should be considered in future studies evaluating the benefit of surveillance following curative cancer resection.