bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between inflammatory markers and prognosis in resected pancreatic cancer (PC).
Authors: Riesco Martinez Maria Carmen , Pernaut Sanchez Cristina , Adeva Alfonso Jorge , Gomez-Martin Carlos , Lema Laura , Luis Robles Diaz , Parrilla Rubio Lucia , Blazquez Arroyo Maria , Merida Garcia Antonio , Lopez-Martin Jose A.
Published: February 2017

250

Background: Inflammatory markers like the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) or fibrinogen (F) and nutritional markers like albumin (alb) have a prognostic value in different types of cancer. However, the paucity of data in pancreatic cancer (PC) keeps their role in this setting unclear. We aimed to determine whether NLR, PLR, F and alb may be prognostic factors in resectable PC. Methods: Demographic, histologic and serologic characteristics (pre and postoperative blood counts) of 77 consecutive PC patients (pts),who underwent curative surgery at our centre between January 2003 and December 2013,were retrospectively collected. We investigated the association of presurgical NLR, PLR, F and alb with overall survival (OS) and disease free survival (DFS) and analyzed the impact of their kinetics after surgery on the outcomes. Results: main pts characteristics are showed in Table. Median OS and DFS were 23 months (m), (95% CI 13.4-32.5) and 10 m (95% CI 7.4 - 12.6) respectively. Pts with NLR < 5 had a significant improvement in OS compared to those with NLR > 5 (29 m vs.16 m, log rank p <0.05 ). F values < 450 mg/dl were also associated with increased OS (30 vs. 16 m, log rank p=0.032). After adjusting by the Cox regression model, only NLR remained an independent prognostic factor for OS (HR, 1.6; p<0.05). PLR (grouped in 3 cutoffs: < 150, 150-300 and >300) and alb (<2, 2-3.5, >3.5 mg/dl) were not associated with significant differences in outcomes. Pre and postoperative values were compared. No association was found between a drop on NLR to <5 after surgery and OS or DFS. Conclusions: our results support that NLR could be a prognostic factor in PC pts undergoing surgery. Changes in NLR due to surgery do not seem to impact the outcome. PLR, F and alb did not correlate with prognosis. [Table: see text]
Clinical implication of peritoneal cytology in the pancreatic cancer patients who underwent curative resection followed by adjuvant gemcitabine or s-1 chemotherapy.
Authors: Katayama Yusuke , Aoyama Toru , Murakawa Masaaki , Asari Masahiro , Yamaoku Koichiro , Kanazawa Amane , Higuchi Akio , Shiozawa Manabu , Ueno Makoto , Morimoto Manabu , Akaike Makoto , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Morinaga Soichiro
Published: February 2017

252

Background: The clinical implications of peritoneal lavage cytology (CY) status in the patients who received curative resection and adjuvant chemotherapy have not been established. The clinical implications of peritoneal lavage cytology (CY) status in the patients who received curative resection and adjuvant chemotherapy have not been established. Methods: We retrospectively analyzed clinical data from 143 consecutive patients who underwent macroscopically curative resection and received adjuvant gemcitabine or S-1 chemotherapy for pancreatic cancer from 2005 to 2014 in our institution. Correlations between CY status and survival and clinicopathological features were investigated. Results: Of the 143 patients, 21 patients were peritoneal washing cytology positive (CY+) (14.7%). Although significant difference was observed in the tumor size, no other correlation between cytology status and clinicopathological parameter existed (age, gender, histology, UICC T status, LN metastasis, lymphovascular invasion). The recurrence free survival (RFS) rates at 3 and 5 years after surgery were 5.1% and 0% in CY+ patients, respectively, and were 21.5% and 16.1% in peritoneal washing cytology negative (CY-) patients, respectively, which were significantly different (p<0.001). On the other hands, the OS rates at 3 and 5 years after surgery were 17.1% and 8.6% in CY+ patients, respectively, and were 26.1% and 16.1% in CY- patients, respectively, which were trend to worse in the CY+ patients. However, there was not significantly different (p=0.254). Conclusions: The patients with CY+ are likely to experience recurrence, even after they received curative resection and adjuvant Gemcitabine or S-1adjuvant chemotherapy. To improve the patient’s survival, it is necessary to develop efficient treatment for CY+ patients.
Significance of serum interleukin-6 in patients treated with radiotherapy for hepatocellular carcinoma.
Authors: Cha Hyejung , Lee Eun Jung , Seong Jinsil
Published: February 2017

254

Background: Interleukin-6 (IL-6) is reported to contribute to aggressive tumor growth and resistance to treatment. In several cancers including esophagus, head and neck, and pancreas, high IL-6 is associated with poor treatment outcome after radiotherapy (RT). However, reports about significance of IL-6 in RT for HCC were rare. The aim of this study was to investigate the significance of serum IL-6 with treatment outcome in patients treated with RT for HCC. Methods: For patients treated with RT for HCC, blood samples were collected prospectively, before start and after completion of RT schedule. Serum IL-6 levels were measured with enzyme-linked immunosorbent assay kit. Patients’ clinical profiles were recorded. Results: Between September 2008 and October 2009, 51 patients were included in this study. Median follow-up duration was 12.3 months (range, 0.5-62.3). Baseline serum IL-6 level was 31.63 pg/ml and patients who had treatment history before RT showed higher baseline serum IL-6 levels than treatment (Tx)-naïve patients (53.09 vs. 15.35, p=0.028). Baseline IL-6 levels were higher in patients showing infield failure (59.70 vs. 14.96, p=0.022) and extrahepatic failure (40.50 vs. 17.88, p=0.072). In patients who had treatment history before RT, higher baseline IL-6 levels were associated with both infield and extrahepatic failure (p=0.014, p=0.032, respectively) in. However, this significance was not found in Tx-naïve patients. Higher baseline IL-6 levels were associated with short infield PFS (p<0.0001) in entire patients and in patients who had treatment history before RT. After RT, serum IL-6 level decreased but it was not significant (29.54 pg/ml, p=0.794). And variation of serum IL-6 level was not associated with treatment failure. Conclusions: Baseline serum IL-6 levels seem significant in predicting treatment outcome in patients treated with RT for HCC. High baseline serum IL-6 levels were associated with infield and extrahepatic failure, especially in patients who had treatment history before RT.
Accuracy of diagnosing pancreatic ductal adenocarcinoma by EUS-FNA at a single institution.
Authors: Beal Hannah , Shea Jill E. , Witt Benjamin , Adler Douglas G. , Mulvihill Sean J. , Downs-Kelly Erinn , Firpo Matthew A. , Scaife Courtney L.
Published: February 2017

258

Background: Endoscopic ultrasound-directed fine needle aspiration (EUS-FNA) in combination with imaging is currently the standard preoperative diagnostic method for pancreatic ductal adenocarcinoma (PDA). Previous studies have reported sensitivities and specificities ranging from 80%-90% and accuracies of approximately 85%. Our goal was to determine the accuracy of EUS-FNA for detecting PDA in individual patients at our institution. Methods: We conducted a retrospective chart review using the Clinical Cancer Research Database at Huntsman Cancer Institute (HCI). We included all cases in which pancreatic lesions were evaluated by EUS-FNA and a subsequent surgical resection was performed. All patients that met these criteria at HCI between March 1999 and April 2014 were included. Descriptive variables were calculated by comparing EUS-FNA results to final surgical diagnoses. The variables used to determine these values were; false positive = PDA by EUS-FNA and negative at resection, true positive = PDA for both, false negative = negative for PDA at EUS-FNA and positive at resection, true negative = negative for both. We considered atypical cells positive for PDA since their presence mandates aggressive intervention by the treating clinician. Results: Of the 242 patients that met the inclusion criterion, 139 were female with an average age of 58 +/- 15 (mean +/- standard deviation) and 103 were male with an average age of 62 +/- 13. In terms of diagnosing PDA by EUS-FNA we determined the sensitivity 89% (81%-94%; 95% confidence interval), specificity 76% (68%-83%), positive predictive value of 74% (66%-82%), and negative predictive value 89% (82%-94%). Conclusions: Although our findings are relatively consistent with the current literature, there is discernible potential for inappropriate treatment of patients based purely on EUS-FNA evaluation. Limitations of this study are the appraisal at a single institution and the necessity to evaluate only cases that ultimately had surgical resection of the pancreatic lesion.
Association of pancreatic metastasectomy for melanoma with long-term overall survival: A single-institution experience.
Authors: Doepker Matthew , Juan TzuHua , Chen Dung-Tsa , Nguyen Phuong , Sarnaik Amod , Pimiento Jose Mario , Hodul Pamela Joy , Malafa Mokenge Peter
Published: February 2017

264

Background: Isolated metastatic melanoma to the pancreas is extremely rare. A recent pooled analysis evaluated 11 patients(pts) with metastatic melanoma to the pancreas and reported a median disease free interval(DFI) between the diagnosis of the primary cancer to the diagnosis of the isolated pancreatic metastasis of 48 months and a 5-year overall survival(OS) of 27%. The purpose of this study was to review our experience with resection of metastatic melanoma to the pancreas and compare it to the more common metastatic renal cell carcinoma(RCC) to the pancreas. Methods: Pts with pancreatic metastasis followed by metastasectomy were identified at a single institution from 1998 to 2013. The Kaplan-Meier method was used to report 5-year OS and disease-specific survival (DSS). Results: We identified24 pts with isolated metastasis to the pancreas that underwent curative resections. Eighteen (75%) were males and the overall median age was 64. Eleven RCC (45.8%), 4 melanomas (16.7%), and 9 other histologies (37.5%) were noted. The median DFI between the diagnosis of the primary cancer to the diagnosis of the isolated pancreatic metastasis for RCC, melanoma, and other histologies was 91.3 months (range, 2.0-361.6), 77.8 months (range, 65.3-97.4), and 55.4 months (range, 7.6-154.8) respectively. Nineteen distal pancreatectomies (79.2%) and 5 pancreaticoduodenectomies (20.8%) were performed. Five-year OS and DSS were 51% and 65%. Pts with metastatic melanoma to the pancreas had a 5-year OS of 67% (95% CI=0.05, 0.95) compared to 65% and 30% for RCC and other histologies respectively. The 5-year DSS for pts with melanoma was 67% (95% CI=0.05, 0.95) vs 100% for RCC and 34% for other histologies. After a median follow up of 39.9 months, all melanoma pts recurred after resection, with a median time to recurrence of 17.7 months. Of the 24, 10 died of disease. Conclusions: We report the largest series on pancreatic metastasectomy for melanoma. Our data show comparable DFI and survival to RCC, along with higher OS compared to previously reported data. Pancreatic metastasectomy for melanoma should be considered as evidenced by prolonged DFI and higher OS.
Initial evaluation of patients diagnosed with pancreatic cancer within a community health system.
Authors: Chen Kathryn Tzung-Kai
Published: February 2017

269

Background: The management of pancreatic patients who are referred to a tertiary care center is well described. However, many patients receive their initial evaluation and care at community health systems. We sought to describe how patients present within the community, the patterns of initial evaluation, and the impact on management. Methods: In a period spanning 3 years (2010-2013), 82 patients were newly diagnosed with pancreatic cancer, as identified by a cancer registry at a community health system. Under IRB approval, data regarding patient characteristics, initial evaluation, and management were retrospectively collected from the electronic medical record (EMR) and analyzed. Results: Of the 82 patients, 68 patients had sufficient data available in the EMR for analysis. Thirty-two patients (47%) initially presented to outpatient clinic, and 36 patients (53%) presented to the emergency department. The presenting complaint was identified as abdominal pain in 33 patients (49%), jaundice in 20 patients (29%), and general malaise in 9 patients (13%). Patients who presented through outpatient clinic vs. emergency department received similar initial imaging studies upfront, including CT of the abdomen and pelvis (61% vs. 72%) and abdominal ultrasound (27% vs. 17%). Sixteen percent of those patients evaluated in outpatient clinic were subsequently admitted, compared to 94% of those patients evaluated in the emergency department. Finally, 31% of those presenting in outpatient clinic eventually underwent surgical resection, compared to 8% of those presenting through the ER, and the median time to surgery for the entire cohort was 1.1 months. Conclusions: Within the community, half of all patients present through the emergency department, and the majority of these are admitted for work up and management of symptoms. In contrast, those patients who present through outpatient clinic are less likely to be admitted, and are more likely to undergo definitive resection. This likely represents a disparity on several levels: the acuity of patients presenting to the emergency department vs. clinic, and how they are managed in each setting.
The efficacy of prophylactic GCSF for FOLFIRINOX.
Authors: Terazawa Tetsuji , Goto Masahiro , Takahiro Miyamoto , Asaishi Ken , Shimamoto Fukutaro , Kuwakado Shin , Nishitani Hitoshi , Kii Takayuki , Higuchi Kazuhide
Published: February 2017

274

Background: Granulocyte Colony-Stimulating Factors (GCSF) is used as supportive care in cancer management when patients (pts) receive chemotherapy with high risk of febrile neutropenia (FN). Peg-GCSF is unapproved in Japan at the time of Aug 2014. Hence, phase II study of combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) for Japanese pts with advanced pancreatic cancer showed FN; 22% and severe neutropenia; 77.8%. Purpose of this retrospective study was to describe the incidence of FN and severe neutropenia during the first cycle of FOLFIRINOX with prophylactic GCSF (pGSF). Methods: Between January 2014 and August 2014, the pts who received FOLFIRINOX with pGCSF were examined retrospectively. The adverse events and detail of pGCSF administration during first cycle were investigated. Results: Among five pts administered FOLFIRINOX, 4 pts received pGSF in first cycle. All patients received FOLFIRINOX without dose reduction. The patient characteristics were as follows: median age (range), 58 (50-66); male/ female, 3/1; PS 0/1, 1/3. The detail of UTG1A1 (*6/ *28) was as follows: (wild type/ wild type), 2pts; (wild/ hetero), 1pt; (hetero/ hetero), 1pt. Hematological adverse events (grade 1/2/3/4) were as follows: leukopenia (0/1/2/0), neutropenia (0/1/0/1), thrombocytopenia (0/4/0/0), FN (0/0/1/0). The patient who occurred grade4 neutropenia and grade3 febrile neutropenia had UTG1A1 *6 hetero/ *28 hetero. Non-hematological adverse events (grade 1/2/3/4) were as follows: elevated GOT (2/1/0/0), elevated GPT (2/1/0/0), elevated T-Bil (0/0/0/0), anorexia (1/2/1/0), fatigue (2/1/0/0), nausea (0/1/2/0), diarrhea (1/1/0/0). The median starting date of pGSF administration was 4.5 (3-7). The median number of pGSF administration was 7.5 (6-9). Conclusions: Although this was retrospective and small study, pGSF appeared to be effective for prevention of severe neutropenia and FN. Hence pGSF might increase dose intensity of FOLFIRINOX.
Comprehensive multiplatform biomarker analysis of 313 hepatocellular carcinoma to identify potential therapeutic options.
Authors: Abou-Alfa Ghassan K. , Miura John Thomas , Gamblin T. Clark , Xiu Joanne , Millis Sherri Z. , Gatalica Zoran , Reddy Sandeep K. , Ang Celina , Yee Nelson S.
Published: February 2017

283

Background: Effective treatment strategies for hepatocellular carcinoma (HCC) remain limited. Identification of additional therapies remains paramount as currently available agents have resulted in marginal improvements in overall survival. Methods: 313 HCC sampleswere evaluated using a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ), including gene sequencing (Sanger, NGS [N=79]), protein expression (IHC) and gene amplification (ISH). Results: Biomarker changes of interest are shown. See Table. TP53 was mutated in 28%, CTNNB1 in 23%, and BRCA2 in 20%; other gene mutation rates were < 5%.TP53-mutated tumors show significantly higher TOPO2A (89% vs. 39%, p<0.0001), TS (70% vs. 32%, p=0.0067) and RRM1 expression (40% vs. 12%, p=0.017), implying high rates of proliferation and DNA synthesis. CTNNB1-mutated tumors showed significantly higher SPARC (67% vs. 21%, p=0.0013) and AR expression (53% vs. 22%, p=0.025). Primary HCC (N=209) exhibited significantly higher PD-1 (89% vs. 33%, p=0.01) and TS expression (35% vs. 13%, p<0.0001) than metastatic (N=105). Patient history/outcomes relative to biomarker status are being evaluated. Conclusions: These data suggest potential therapeutic targets, such as tyrosine kinase inhibitors, anti-PD1 agents, or PI3 kinase pathway inhibitors. Although no evidence shows that cytotoxics are effective in patients with HCC, irinotecan, alkylating agents, fluoropyrimidines, anthracyclines, nab-paclitaxel, gemcitabine, or taxanes may be therapeutically relevant. The protein changes associated with CTNNB1-mutated tumors suggest potential benefit of targeting WNT pathway in combination with nab-paclitaxel or anti-androgens. Immuno-modulatory agents may be a therapeutic option in primary HCC, based on the higher levels of PD-1. Multiplatform tumor profiling reveals molecular heterogeneity HCC, similar overall to previous reports, and identifies different potential treatment options for molecular subtypes. [Table: see text]
Neuroendocrine gene transcript analysis of blood to define the completeness of surgical resection and identify stable or progressive neuroendocrine tumor disease.
Authors: Kidd Mark S. , Modlin Irvin Mark , Frilling Andrea , Alaimo Daniele , Callahan Stephen , Bodei Lisa , Drozdov Ignat
Published: February 2017

293

Background: A critical requirement in NET management is a sensitive, specific, reproducible blood biomarker test. Surgery and somatostatin analogs (SSAs) are widely used but efficacy is difficult to determine. Imaging is relatively insensitive for residual/recurrent disease determination and symptoms remains the only way to determine SSA efficacy. We evaluated a PCR-based 51 transcript signature (NETest) comparing it to CgA to determine whether biomarkers were effective in defining surgical resection and SSA efficacy. Methods: GEP-NETs (n=50) [M:F 19:31; median age: 58 years, small intestine: n=35, pancreas n=9, rectum n=3, appendix: n=2, stomach n=1] were evaluated. Groups included surgery (n=15, R0-no disease), and SSA therapy (n=35). qRT-PCR was used for transcript measurement, ELISA (DAKO) for CgA and imaging (RECIST) for clinical status. NETest defined risk of disease activity (low disease activity risk <47%, high risk 47-100%). Results: Resection decreased NETest (pre-surgery: 80±6%; 1 post-surgery: 29±6%, p<0.0001). Thirteen (87%) were high risk before surgery; post-surgery two (13%) remained high risk (despite lowered score), 11 (74%) were low risk and 2 normal. Four (26%) developed recurrence at 6 months. CgA levels were non-informative. In the SSA group, the NETest was lower in clinically stable disease (32±3.7%; n=25) than in progressive disease (82±4.3%, n=10; p<0.0001). All patients in the latter were categorized as high risk disease activity. The accuracy for differentiating stable from active disease was 92% (sensitivity=100%, specificity=88%). Three SSA patients developed clinically progressive disease with concordant increases in NETest. CgA levels were not significant and were non-informative. Conclusions: NET transcript analysis accurately defined surgical cytoreduction and identified biochemical evidence of residual disease. NETest also accurately identified stable and progressive clinical disease activity during SSA treatment. Blood-based multigene analytic measurement will facilitate early detection of residual/recurrent disease and further define therapeutic efficacy for surgery and SSAs.
Effect of targeting tumor-infiltrating myeloid cells on tumor progression in pancreatic adenocarcinoma.
Authors: Nywening Timothy M. , Belt Brian , Cusworth Brian M , Panni Roheena Z. , Sanford Dominic E. , Goedegebuure Peter S. , Linehan David
Published: February 2017

298

Background: Human pancreas cancer (PC) is associated with a heavy desmoplastic reaction and influx of bone marrow derived myeloid cells. Recruitment of these cells by the tumor allows for PC to create a favorable microenvironment that is immunosuppressive. Our work demonstrates that the most abundant type of myeloid cell in PC is granulocytes, which are positive for the chemokine receptor CXCR2. This receptor is vital for the trafficking of granulocytes from the peripheral blood to the tumor, therefore selective targeting of these cells via CXCR2 blockade may lead to potential clinical benefit in patients with PC. Methods: Human samples were obtained under IRB approved protocol at Washington University.C57BL/6 mice were injected subcutaneously or orthotopically with syngeneic PC (KCKO) cells and treated with vehicle or inhibitor daily. Tumor size was determined by caliper measurements and weight. Flow cytometry was performed and samples analyzed for myeloid markers. Results: Human PC patients have elevated levels of CXCR2+ granulocytes in the peripheral blood (p=0.02) and tumor microenvironment (p=0.002) compared to controls. In a murine model, CXCR2 inhibition reduces tumor infiltrating granulocytes (p=0.02) which was associated with a reduction in tumor growth in both a subcutaneous and orthotopic model (p=0.03). Our group has previously demonstrated that targeting the monocytic subset of myeloid cells in PC is an effective treatment strategy (p=0.02). Surprisingly, neither antagonist alone was effective at significantly decreasing the total tumor myeloid infiltrate and treatment with CCR2 inhibitor alone increased tumor infiltrating granulocytes (p=0.03). However, both therapies in combination resulted in a significant reduction in total tumor myeloid infiltrate (p<0.05) and was synergistic in regards to tumor reduction compared to either therapy alone (p<0.05). Conclusions: Human PC has an abundant CXCR2+ granulocytic infiltrate and blockade of CXCR2 may translate to potential clinically useful therapies.
Targeting the Rho-ROCK pathway to treat pancreatic cancer: The use of unique preclinical models to ascertain the effects on cancer growth and metastasis.
Authors: Chin Venessa T. , Conway James , Nagrial Adnan , Chantrill Lorraine A. , Chou Angela , Steinmann Angela , Gill Anthony , Pinese Mark , Wu Jiamin , Johns Amber , Dury Alison , Biankin Andrew , Timpson Paul , Pajic Marina
Published: February 2017

312

Background: Pancreatic cancer (PC) is a highly lethal and genetically heterogenous disease. Genomic sequence data from the Australian Pancreatic Cancer Genome Initiative (APGI) has identified a subset of patients with ROCK-1 amplification. ROCK-1 is a downstream target of Rho, a small GTPase that plays an important role in regulating proliferation, invasion and metastasis of cancer cells. Our aim was to analyse the effects of inhibiting ROCK-1 using specific small molecule inhibitors (Fasudil and Y-27632) in well annotated and robust pre-clinical model systems generated as part of our APGI efforts. Methods: Patient derived cell lines (PDCL) and xenografts (PDX) were used to test the effectiveness of ROCK-1 inhibitors (RI). Colony formation and 3-D organotypic assays tested cellular proliferation and invasion. In vivo, pre-clinical trials assessed the effect gemcitabine (G) +/- RI on a range of PDXs with varying tumour ROCK expression, including one G resistant model. A PDCL shown to form metastases when injected orthotopically into mice has been labeled with firefly luciferase. The effect of RI on metastasis formation will be assessed in vivo using real time imaging. Results: ROCK inhibition has a differential effect on colony formation on PDCLs in vitro, and inhibits cellular invasion. A statistically significant increase in median survival in the G + RI group compared with G alone, was seen in 3 PDXs, including the G resistant tumour. 1 PDX showed a decrease in tumour size at 200 days in the G + RI group. Conclusions: ROCK inhibition has a differential effect in vitro, but an anti-tumour effect in vivo, including overcoming resistance to G. This suggests that effects on the tumour micro-environment are an important mechanism of action. RI have the potential to be an effective therapy in PC.
Amrubicin monotherapy for patients with platinum-refractory gastroenteropancreatic neuroendocrine carcinoma.
Authors: Ando Takayuki , Hosokawa Ayumu , Yoshita Hiroki , Ueda Akira , Kajiura Shinya , Mihara Hiroshi , Nanjo Sohachi , Fujinami Haruka , Nishikawa Jun , Sugiyama Toshiro
Published: February 2017

328

Background: Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, because studies on salvage chemotherapy are limited, its role remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC. Methods: Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2006 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively. Results: Eight males and two females ((median age, 67 years (range, 52–78)) received platinum-based chemotherapy, including cisplatin plus irinotecan (n = 7, 70%), cisplatin plus etoposide (n = 2, 20%), and carboplatin plus etoposide (n = 1, 10%) before amrubicin therapy. A total of 30 cycles of amrubicin was administered in 10 patients, with a median number of cycles per patients was 2.5 (range, 1-7). Median progression-free survival (PFS) and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Two patients with partial response had characteristics of NEC with a high Ki-67 index (99% and 89%, respectively) and had received cisplatin and irinotecan as first-line treatment. Grade 3–4 neutropenia and anemia were observed in four (40%) and five (50%) patients, and they were manageable in all cases by careful monitoring of myelosuppression and appropriate dose reduction of amrubicin. Conclusions: Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.
The antitumor effect of epigallocatechin-3-gallate on gastroenterological cancer.
Authors: Iwahashi Shuichi , Shimada Mitsuo , Morine Yuji , Imura Satoru , Ikemoto Tetsuya , Arakawa Yusuke , Saito Yu , Yamada Shinichiro , Yismaw Gizachew
Published: February 2017

335

Background: Green tea is one of the most popular beverages it contains many catechins such as epigallocatechin-3-gallate (EGCG) inhibits cancer growth. The aim of this study was to elucidate the anti-tumor effect and the effect for spheres of EGCG. Methods: Human hepatoma-derived cell line (HepG2) and human colorectal carcinoma cell line (HCT-116) were used. The anticancer effects of EGCG was studied by MTT assay. We made cancer sphere from HepG2 cells, and we added EGCG to cancer sphere. And we compared the gene expressions of RT-PCR between normal HepG2 and cancer sphere groups. Results: EGCG had the anti-tumor effect in dose-dependent. Furthermore, EGCG cancelled this spheroid formation, EGCG down-regulated the Nanog and CD133, related stemnesss genes. And then, EGCG down-regulated the ABCG1and Nek2, related ABC transporter genes, expression in sphere. Conclusions: EGCG had the anti-tumor effects on gastroenterological cancer, and EGCG had the effect to sphere, same as cancer stem cell thorough the down-regulation of ABC transporter related genes. Therefore, EGCG might be used as the safe and novel antitumor agents.
Gastrointestinal metastases from melanoma: Does surgical resection improve survival when performed in combination with immunotherapy?
Authors: Deutsch Gary B. , Kirchoff Daniel D. , Bailey Mariel , Vitug Sarah , Flaherty Devin C. , Foshag Leland Jay , Bilchik Anton , Faries Mark B.
Published: February 2017

340

Background: Prior studies have shown the benefits of metastasectomy and more recently, immunotherapy, in Stage IV melanoma. We report the largest series of gastrointestinal (GI) melanoma metastases, in order to clarify the role of surgical resection in the setting of systemic treatment options. Methods: A review of our institutional melanoma database identified all patients with hollow viscus GI metastases diagnosed between 1971 and 2013. Patient age and sex; primary tumor location, thickness and ulceration; GI-metastasis free interval; and types of treatment were analyzed. The primary endpoint was melanoma-specific survival (MSS), measured from the diagnosis of GI metastases. Survival analyses compared combination therapy to immunotherapy (i.e. vaccine, interleukin-2, interferon, ipilimumab) or surgery alone. Operative patients were further stratified by surgical intent (curative or palliative). Results: The 393 study patients had a median GI-metastasis free interval of 49.5 (0 – 416.0) months from the initial diagnosis; their mean age at GI metastases was of 53.5 ± 14.1 years. Median MSS was 20.0 months with surgery plus immunotherapy (n=160), 13.0 months with surgery alone (n=111), 8.0 months with immunotherapy alone (n=64), and 5.0 months with neither treatment (n=58) (p<0.001). By multivariable analysis, age at GI metastasis diagnosis (HR=1.014; p=.014), truncal melanoma site (HR=1.659; p=.017), immunotherapy (HR=0.675; p=.030), and metastasectomy (HR=0.544; p<.001) were significant predictors of MSS. Surgical intent was known in 98 patients: curative surgery had a median MSS of 30.0 months (n=49) and palliative surgery had a median MSS of 12.0 months (n=49) (p=.015). Conclusions: Treatment of GI melanoma metastases should use a combination of metastasectomy and immunotherapy, instead of either modality alone. Select patients are likely to obtain an enhanced benefit from GI metastasectomy, specifically curative surgery, in the setting of newer immunotherapy options.
Surgical outcomes of patients with pancreatic cancer treated with stereotactic body radiation therapy.
Authors: He Jin , Moningi Shalini , Blair Alex B , Zaki Ahmed , Laheru Daniel A. , Cameron John L. , Pawlik Timothy M. , Weiss Matthew J. , Wolfgang Christopher Lee , Herman Joseph M.
Published: February 2017

341

Background: The surgical outcome of patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BRPC/LAPC) treated with stereotactic body radiation therapy (SBRT) is unclear. Methods: A comparative study was performed to determine if surgical outcomes were different among patients receiving neoadjuvant SBRT vs chemoradiation therapy (CRT) vs chemotherapy only. Results: Between 2011 and 2014, 29 patients with BR/LA-PDAC underwent neoadjuvant chemotherapy and SBRT (6.6 Gy x 5 fractions) followed by pancreatectomy. Eighteen of 29 patients (62%) had LAPC. Their outcomes were compared with 82 patients who received neoadjuvant CRT and 26 patients who received neoadjuvant chemotherapy only (Table). When compared to neoadjuvant CRT and chemo only, the neoadjuvant SBRT group had a higher R0 resection rate (90% vs 84% vs 62%, p=0.02) and vascular resection rate (41% vs 13% vs 31%, p=0.005), respectively. Although the vascular resection and complication rates (Clavien grade 3 or above) were higher in the neoadjuvant SBRT group, no in-hospital mortality was encountered. In the SBRT group, the complete pathological response rate (21%) was higher than that of the other groups (4% and 0% respectively, p<0.001). Survival will be updated later as the current median postoperative follow-up is 6 months in the SBRT group. Conclusions: Neoadjuvant chemotherapy and SBRT is associated with improved surgical outcomes and pathologic complete response rates in selected patients with BRPC/LAPC. Longer follow-up is needed to determine its impact on survival. [Table: see text]
Liver resection and outcome of hepatocellular carcinoma (HCC) in a transplant center.
Authors: Barzi Afsaneh , Cao Shu , Genyk Yuri , Kahn Jeffrey , Wallman Melissa A , El-Khoueiry Anthony B.
Published: February 2017

350

Background: HCC has rising incidence and mortality in the US. Liver transplantation and surgery are the definitive treatment options. The median time to liver transplant in California is longer than many other regions. Given the expertise of our surgeons in liver resection we investigated the outcome of HCC at our institution. Methods: We extracted Norris Cancer registry data for patients (pt) with diagnosis of HCC from 2000 to 2010 who received their initial treatment at our facility. Overall survival (OS) is the primary end point of this study. We classified pt into transplant candidates (TC) vs. non-transplant candidates (NTC) based on the combination of T stage and vascular involvement. Results: We identified a total of 497 pts with HCC (Table). 98 pts had incomplete staging and 20 had metastatic disease and excluded from the analysis. We classified 221 pts as TC and 158 pts as NTC. The median OS for the TC was 2.9 years (yr) (95% CI 2.1-3.9) and in the NTC was 1.4 yr (95% CI 1.1 – 1.6). Amongst TC, 44 received transplant, 33 had surgical resection, and 144 had loco-regional treatment. Transplant recipients had an OS of 9.7 yr versus 4.3 yr (95% CI 1.9-9.1) in surgical patients, those with no definitive treatment had a OS of 1.8 yr (95%CI 1.6 -2.3). Among TC Hispanics had the best OS 4.3 yr (95% CI 1.9 – 9.7), followed by Asians 4.0 (95% CI 2.4-5.8), and Whites 2.0 (95% CI 1.4 -2.7) (p-value 0.0125). Among NTC Hispanics had the best OS 1.8 yr (95% CI 1.3 – 2.6), Asians 1.5 (95% CI 1.0 -2.1), and Whites 1.0 (95% CI 0.7 -1.4) (p-value 0.079). Conclusions: Liver transplantation continues to offer the best survival outcomes; however, in a region with long wait times, surgical resection offers a reasonable alternative with favorable survival outcomes. The trend of superior survival amongst Hispanics is noteworthy and subject of further investigation at our center. [Table: see text]
Characterization of HER2 testing and treatment patterns among patients with gastric cancer in the United States using the Oncology Services Comprehensive Electronic Records (OSCER) database.
Authors: Lowe Kimberly A , Reich Adam , Bobiak Sarah , Chau Dina , Quigley Jane M , Kelsh Michael A.
Published: February 2017

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Background: There is a paucity of data related to HER2 testing and treatment patterns among gastric cancer patients in a real-world setting. Our primary objectives were to (1) identify the proportion of gastric cancer patients who received HER2 testing, the proportion of patients with HER2+ve tumors, and the proportion of HER2+ve patients who received trastuzumab; (2) describe treatment patterns among gastric cancer patients, including the proportion of patients who received surgery and/or radiation with chemotherapy; (3) identify the proportion of patients who received singlet, doublet, or triplet chemotherapy treatments and specific first- and second-line regimens. Methods: The study participants were randomly selected to undergo a detailed chart review from a source population of patients included in the OSCER database who were diagnosed with gastric cancer from 2009 to 2013. OSCER is a data warehouse of electronic medical records from 565 community and hospital-affiliated oncology clinics in the U.S. from 2004 forward. All patients were required to have metastatic gastric cancer at the time of the chart review and have been treated with chemotherapy to be included. Descriptive statistics were used to characterize HER2 testing and treatment patterns. Results: The study patients (n=238) were mostly male (62%), Caucasian (58%), >65 years of age (57%), with the following stage distribution at diagnosis (Stage II: 7%; Stage III: 11%; Stage IV: 63%; unknown: 19%). HER2 testing was documented in n=121/238 (51%), of which n=30/121(25%) were HER2+ve. Among HER2+ve patients, n=20/30 (67%) received trastuzumab. Of the total sample (n=238), 79% were treated with only chemotherapy, 4% received chemotherapy and surgery, 15% received chemotherapy and radiation, and 2% received all three treatments. First-line treatment was as follows: singlet (17%); doublet (33%), triplet (38%), other (12%). Conclusions: Only half of patients were tested for HER2 status; however, the use of trastuzumab among HER2+ve patients was high. Chemotherapy alone was the primary treatment in this population.
Radiotherapy in locally advanced pancreatic cancer: SEER experience.
Authors: Mahipal Amit , Sajjad Monique Z. , Denson Aaron , Shridhar Ravi , Springett Gregory M. , Batra Sachin
Published: February 2017

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Background: Pancreatic cancer is the fourth most common cause of cancer deaths in the US. Despite the fact that the radiotherapy in addition to chemotherapy is frequently employed, the role of radiation therapy in the treatment of locally advanced pancreatic cancer (LAPC) remains controversial. The majority of the data evaluating the efficacy of this approach is derived from small randomized trials. Methods: The Surveillance, Epidemiology and End Results (SEER) registry dataset from 2004-2011 was queried to identify patients with locally advanced pancreatic adenocarcinoma. Pts with survival <2 months, unknown radiation status and those who received post-operative radiation were excluded. Multivariate analysis of prognostic factors related to survival was performed using a Cox proportional hazard regression model. Results: We identified 4,460 patients that met the inclusion criteria; 59% of pts received radiation and 41% did not. The two groups were similar with respect to gender, race and tumor differentiation. Pts in the radiation group were younger (ages<65: 49% vs. 38%), had smaller tumor size (largest dimension <4.5 cm: 80% vs. 75%), lesser lymph node involvement (33% vs. 36%) and lower rate of surgical resection (4% vs. 9%). Radiation treatment, age, tumor grade and surgical resection were significantly associated with survival on univariate analysis. Patients who received radiation therapy had better survival (median OS: 11 vs. 7 months; HR: 0.77; 95% CI 0.69-0.78). On the multivariate analysis, radiation was independently associated with improved survival (Table). Conclusions: In this population-based registry, radiation therapy was associated with improved survival in patients with LAPC in both univariate and multivariate analysis. Larger randomized trials are needed to confirm these findings. The optimal schedule and type of radiation therapy remains unknown. [Table: see text]
Evaluation of liver toxicity using Child-Pugh, MELD, and MELD-Na following stereotactic body radiation therapy (SBRT) of hepatocellular carcinomas.
Authors: Lu Louis , ElAlfy Eman , Wahl Daniel , Stenmark Matthew H. , Lawrence Theodore Steven , Feng Mary Uan-Sian
Published: February 2017

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Background: Radiation-induced liver disease (RILD) has been tracked when assessing the safety of fractionated liver radiotherapy. However, due to the rarity and severity of events, a more sensitive measure of liver damage is necessary. This study characterizes the time course of changes in generalizable measures of liver function as potential toxicity metrics. Methods: In this IRB-approved retrospective study, the records of 63 patients with 87 HCC tumors treated with SBRT at the University of Michigan between 2006 and 2012 were reviewed. Changes in Child-Pugh (CP), MELD, and MELD-Na were analyzed using the Student t test and chi-squared test. Results: 83% of the patients had cirrhosis, 62% hepatitis (hep) C, 7% hep B, 25% alcoholic, and 13% other. 83% had prior liver-directed therapy. 24% had >1 tumor concurrently treated with SBRT. Median tumor size was 2.3 cm (0.7-10), gross tumor volume was 9.2 cc (0.6-469), and mean liver dose-GTV was 4.4 Gy (0-17.6 Gy). Prior to SBRT, 73% were CP A, 25% CP B, and 2% CP C. Median baseline CP, MELD, and MELD-Na were 5, 9, and 10. Mean CP increases after 3, 6, 9, and 12 months were 0.84, 1.79, 1.72, and 1.33; increases in MELD 1.47, 2.88, 5.38, and 3.91; increases in MELD-Na 1.45, 2.03, 4.24, and 2.48. All changes were significantly increased from baseline. On univariate analysis, >1 tumor and cirrhosis predicted for a 1+ point increase in CP and >1 tumor and higher mean liver dose-GTV for a 2+ point increase in CP. Older age, >1 tumor, smaller GTV, and smaller max tumor dimension predicted for a 10+ point increase in MELD and >1 tumor, hep C cirrhosis, and higher baseline MELD-Na for MELD-Na. Patients treated concurrently to >1 tumor had greater increases in CP (3.60 vs. 0.81), MELD (9.33 vs. 1.97), and MELD-Na (8.47 vs. 2.19), p < 0.0001 for all, compared to those with 1 tumor. No differences were seen with gender, portal vein thrombosis, number of prior treatments and baseline Child-Pugh classifications. Conclusions: We describe a time course and predictive factors for change in CP, MELD, and MELD-Na scores after SBRT for HCCs. These should be investigated further for potential use in toxicity modeling after incorporating dosimetric parameters.
The incidence and clinicopathologic features of metachronous gastric tumors after endoscopic submucosal dissection.
Authors: Park Sung Won , Lee Yun Ho , Kim Dae Young , Bae Song I , Yoon Won Jae , Ryu Soo Hyung , Kim You Sun , Moon Jeong Seop
Published: February 2017

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Background: Endoscopic submucosal dissection (ESD) has become a standard method of treatment for gastric tumors. The synchronous and metachronous development of two or more primary adenocarcinomas occurs in 10 to 20% of all cases of stomach cancer. Therefore, metachronous recurrence should be a consideration after ESD has been performed. The aim of this study was to review our experiences in the management of patients with synchronous and metachronous lesions, and to evaluate their incidence and clinicopathologic features. Methods: We reviewed 194 patients who underwent ESD for gastric tumors between January 2007 and December 2011. Synchronous lesions were defined as secondary gastric tumors detected within 6 months after the initial ESD. Metachronous tumors were defined as those detected more than 6 months after the initial ESD. We investigated the incidence and clinicopathologic features of synchronous and metachronous tumors after ESD. Results: In total, 20 patients (10.3%) had synchronous lesions and 19 patients (9.8%) had metachronous lesions. The annual incidence of metachronous tumors after ESD was 2.93%. The median period until discovery after initial ESD was 40.1 months. Female patients developed synchronous and metachronous tumors more frequently than male patients (p = 0.037). Patients with H. pyloriinfections developed tumors more frequently than those without (p = 0.04). There were no significant differences with respect to the type and differentiation of tumors. Conclusions: Synchronous and metachronous lesions of gastric tumors were considerably prevalent after ESD. Considering the results of this study, careful endoscopic investigation should be performed after ESD for female patients and those with H. pylori infections. However, further large-scale and longer prospective studies are needed.
Utilizing Ki67 score to predict optimal liver-directed treatment in patients with metastatic neuroendocrine tumors.
Authors: Singla Smit , Attwood Kristopher , Levea Charles , Tomaszewski Garin , Kuvshinoff Boris W. , Iyer Renuka V.
Published: February 2017

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Background: Patients with metastatic neuroendocrine tumors (NETs) benefit from treatment with yttrium-90 radioembolization (Y-90) or transarterial chemoembolization (TACE), however the criteria for patient selection are not well defined. We sought to determine if the proliferative index (Ki67 score) could be utilized to select patients for one therapy over the other. Methods: A single institution analysis of all patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 scoring, and the data was analyzed using multivariate association for survival outcomes. Results: Amongst 72 patients (M: 39, F: 33; median age, 57 years) included in the study, the most common site of tumor origin was small bowel (n=35, 49%), and the most common histology subtype was carcinoid (n=58, 85%). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) in the TACE group. In Y-90 group, there was a higher concomitant use of sandostatin (94% vs 75%, p=0.023), longer time between diagnosis and treatment (median, 32 vs 11 months, p=<0.001), and less number of total treatments completed (89% vs 46%, p<0.001). There was no significant difference in overall survival (OS) between the groups (median, 69 vs 82 months, respectively; p=0.477); however when adjusted for Ki67 score of 3, patients with Ki67 score >3% were found to have better OS when treated with Y-90 as compared to TACE (HR, 0.083; CI, 0.008-0.854). On the other hand, in patients with Ki67 <3%, OS was better when treated with TACE (HR, 13.5; CI, 1.2-148.8). Further, patients in Y-90 group had higher incidence of carcinoid syndrome (39% vs 21%, p=0.195) and bilobar liver disease (95% vs 89%, p=0.371), whereas hepatic tumor burden >25% was greater in the TACE group (26% vs 20%, p=0.614), but these differences were not significant. Conclusions: In patients with metastatic NETs, Ki-67 score >3% may be predictive of treatment benefit with Y-90 and <3% with TACE. A longer time from diagnosis and an increased number of prior therapies may indicate a need for aggressive therapy; however a prospective validation is warranted.