bluuebunny/crossref_metadata_2025 huggingface dataset:
Resectability and indication for chemotherapy in patients with colorectal liver metastases as assessed by medical oncologists and surgeons.
Authors: Homayounfar Kia , Bleckmann Annalen , Helms Hans-Joachim , Lordick Florian , Rüschoff Josef , Conradi Lena-Christin , Sprenger Thilo , Lorf Thomas , Becker Heinz , Ghadimi B. Michael , Liersch Torsten
Published: March 2020

e14167

Background: Multidisciplinary treatment in patients with colorectal liver metastases (CRLM) is standard in modern oncology. However, for interdisciplinary discussion assessing complimentary disciplines' potential and changes in personal views is crucial. We evaluated experienced medical oncologists' (MO) and surgeons' (SG) assessment of resectability and indication for chemotherapy (CTx) in patients with CRLM. Methods: Thirty patients who underwent R0-resection of CRLM between 2001 and 2011 at our department were selected. Medical history and staging data were presented to MO (n=10) and SG (n=11) in a virtual tumor board (TB1). Standardized blinded TED-voting answers (9 options) included assessment of resectability and the indication for pre- and/or postoperative CTx. The virtual tumor board was followed by training in terms of state-of-the-art lectures on potential of CTx and surgery. Assessment was then repeated in a second virtual tumor board (TB2). Results: 630 (21x30) answers were obtained per tumor board. In TB1 resectability, borderline resectability and definite unresectability were expected in 433, 161 and 36 answers, respectively. Resectability was significantly more often expected by SG (p<0.001). In TB2 57% of answers were different from TB1 (p<0.001). Assessment shifted from borderline resectable to resectable CRLM in 81 of 161 and from unresectable to (borderline) resectable CRLM in 29 of 36 answers (p<0.001). The shift was significant in MO (p=0.012) and SG (p<0.001). Preoperative CTx was significantly more often indicated by MO (p=0.041) and included in 255 answers (44%) in TB1 compared to only 157 answers (27%) in TB2 (p<0.001). With 55% of answers voting for postoperative CTx remained stable in TB1 and TB2 without a significant difference between MO and SG in either TB1 (p=0.099) or TB2 (p=0.353). Conclusions: Resectability and indication for pre- but not postoperative CTx were discrepantly assessed by MO and SG. Training had a strong influence on decision making in MO and SG resulting in a higher rate of patients deemed (borderline) resectable. Furthermore, following training MO and SG opted less often for preoperative CTx.
Clinical and pathological characteristics of elderly colorectal cancer patients over 70 years old and comparison with patients under 50 years old.
Authors: Erismis Betul , Kucukoztas Nadire , Rahatli Samed , Yalcin Selim , Dizdar Omer , Altundag Ozden , Ozyilkan Ozgur
Published: March 2020

e14174

Background: Incidence of colon cancer increases with age and generally is diagnosed at the age of between 60-75. Because of comorbidities in elderly patients who are older 70 years of age, lower doses of adjuvant or metastatic therapy is given them or the other option can be the chemotherapeutics which had less side effects. Methods: We aim to identify clinical and pathological characteristics of elderly colorectal cancer patients over 70 years of age who were followed at Baskent University Hospital and compare with CRC patients under the 50 years of age. Results: 182 CRC patients were assigned to the study who were followed between 1998-2011. We classified the patients into two categories according to the age. 91 participants were over 70 years of age and 91 participants were under 50 years of age. There were no significant differences between two groups for gender and percentage of patients having surgery (p=0.65/0.732). History of having systemic disease was significantly higher in the elderly group (p<0.001). Adjvuvant chemotherapy was given to the 38 (53.5%) patients aged over 70 and 66 (91.7%) patients aged under 50 (p<0.001). We compared the both groups for progression free and overall survival time for all stages. However, there were no statistically significant differences between two groups. Conclusions: Our study confirms that elderly CRC patients get benefit from the adjuvant chemotherapy treatment as the same as patients under 50 years of age. Therefore, physcians should consider about performance status and systemic disease in elderly patients and give an individual treatment to them.
Extended intersphincteric resection with quadrant resection of external sphincter after neoadjuvant mid-course chemoradiotherapy in the very low rectal cancer.
Authors: Oh Nahmgun , Ko Sanghwa , Kim Hyunsung
Published: March 2020

e14181

Background: To evaluate the results of extended intersphincteric resection of T3 rectal cancer situated below 4cm from the anal verge, comparing the results of simple intersphincteric resection of T2 rectal cancer after mid-course chemoradiotherapy. Methods: Between 2000 Between 2000 and 2006, 67 patients with rectal cancer below 4cm from anal verge, underwent abdomino-intersphincteric resection reconstructed by inversion proctoplasty with a colonic J-pouch and diverting ileostomy. All patients received a total irradiation dose of 30 Gy with conventional fractions for 3 weeks. Capecitabine was administered 1000mg/m2 twice a day on 21 days during radiotherapy, followed curative surgery in a week without resting period. After preoperative radio-chemotherapy, patients with overt T2 lesion were 27 cases (40.3%) and received intersphincteric resection (Group I: simple intersphincteric resection), and patients with borderline cases or T3 lesion were 40 cases (59.7%) and received intersphincteric resection with quadrant resection of upper external sphincter and primary repair of the external sphincter as inversion proctoplasty (Group II: extended intersphincteric resection). Results: The mean patients age was 61.2 years. The mean location of cancer was at 3.2cm from anal verge (2-4cm). Anastomotic leakage was confirmed in 11 patients (16.4%). There was no postoperative mortality. The grade I, II of continence by Kirwan classification was 81.5%, 80.0% in Group I and II. Under 3 times stool frequency per day was 51.9%, 62.5% in Group I and II. Two patients (3.0%) experienced locoregional recurrence of pelvic cavity. 5-year overall survival rate was 83.6%. Conclusions: Simple and extended intersphincteric resection is seemed to be a safe and functionally acceptable procedure. And, neoadjuvant mid-course chemoradiotherapy using oral capecitabine 2,000 mg/m2/day on 21 days during 2 Gy radiation of each 15 weekdays is seemed to be a tolerable and effective modality, in patients with very low rectal cancer.
Influence of blood neutrophil to lymphocyte ratio on oncologic outcomes in peritoneal carcinomatosis of appendiceal origin.
Authors: Idrees Kamran , Luciano Jason , Austin Frances , Sathaiah Magesh , Ramalingam Lekshmi , Jones Heather L , Pingpank James F. , Ahrendt Steven Arthur , Zureikat Amer H , Holtzman Matthew Peter , Zeh Herbert , Bartlett David L. , Choudry Haroon
Published: March 2020

e14184

Background: The Neutrophil to lymphocyte ratio (NLR), a marker of systemic inflammatory response, is associated with prognosis in various cancers. The aim of this study is to evaluate the association of pre-operative NLR with oncologic outcomes in patients with appendiceal carcinomatosis. Methods: Clinico-pathological data were obtained from a prospectively maintained database of patients with appendiceal carcinomatosis who underwent cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemoperfusion (HIPEC) between 2001 and 2010. Pre-operative absolute neutrophil and lymphocyte counts were used to compute NLR, with elevated NLR defined a priori as >5. Logistic regression modeling and Kaplan-Meier analyses were performed on the available data. Results: 195 patients, with a median age of 54.5 years, underwent CRS and HIPEC. The median follow up time was 1.96 years. There were 41 patients (21%) who had elevated NLR preoperatively. Factors associated with overall survival (OS) were grade (p=0.01), simplified peritoneal cancer index (SPCI) (p=0.013), and age (p=0.02). In patients who did not undergo splenectomy at the time of CRS, elevated NLR, lymph node involvement, SPCI, age and pre-operative albumin were statistically significant predictors of OS on multivariable analysis. None of these factors were significant in patients who underwent splenectomy at the time of CRS. The 5-year overall survival was 57% vs. 31% in patients with NLR<5 compared to NLR>5 respectively (p<0.0001). Time to progression was 30 months compared to 14 months in patients with NLR<5 vs. >5 (p=0.001). Strikingly, the 5-year OS in patients with NLR<5 with or without splenectomy was 63% and 50% compared to patients with NLR>5 with or without splenectomy 37.5% vs. 23%, respectively (p=0.0001). Conclusions: In patients with appendiceal carcinomatosis, pre-operative NLR is a potential systemic inflammatory marker that independently predicts oncologic outcomes. The impact of NLR appears to be influenced by the performance of splenectomy at the time of CRS. Further studies will be required to prospectively validate this systemic inflammatory marker and its interaction with splenectomy.
Recursive partitioning for new classification of patients with esophageal cancer treated by chemoradiotherapy.
Authors: Nomura Motoo , Shitara Kohei , Kodaira Takeshi , Kondoh Chihiro , Takahari Daisuke , Ura Takashi , Kojima Hiroyuki , Kamata Minoru , Muro Kei , Sawada Satoshi
Published: March 2020

e14500

Background: The 7th edition of the American Joint Committee on Cancerstaging system does not include lymph node size in the guidelines for staging patients with esophageal cancer. The objectives of this study were to determine the prognostic impact of the largest lymph node diameter (ND) on survival and to develop and validate a new staging system for patients with esophageal squamous cell cancer who were treated with definitive chemoradiotherapy (CRT). Methods: Information on 402 patients with esophageal cancer undergoing CRT at 2 institutions was reviewed. Univariate and multivariate analyses of data from 1 institution were used to assess the impact of clinical factors on survival, and recursive partitioning analysis was performed to develop the new staging classification. To assess its clinical utility, the new classification was validated using data from the second institution. Results: According to RPA, ND stages were best when classified as ND0 (the absence of lymph node metastases), ND1 (< 2.8 cm), and ND2 (≥ 2.8 cm). By multivariate analysis, gender, T, N, and ND stages were independently and significantly associated with survival (p<0.05). The resulting new staging classification showed the following: T1-2ND0 as Group I; T3-4ND0 or T1-2ND1 as Group II; T3-4ND1 as Group III; and TanyND2 as Group IV. The 4 new stages led to good separation of survival curves in both the developmental and validation datasets (p<0.05). Conclusions: Our results showed that lymph node size is a strong independent prognostic factor and that the new staging system, which incorporated lymph node size, provided good prognostic power and discriminated effectively for patients with esophageal cancer undergoing CRT.
A phase II trial of gemcitabine and S-1 therapy in patients with resected pancreatic cancer: Japanese study group of adjuvant therapy for pancreatic cancer (JSAP-03).
Authors: Ishii Hiroshi , Ueno Hideki , Kosuge Tomoo , Matsuyama Yutaka , Saiura Akio , Koga Rintaro , Sakamoto Yoshihiro , Shimada Kazuaki , Nakao Akimasa , Doi Ryuichiro , Tanaka Masao ,   Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer
Published: March 2020

e14506

Background: Gemcitabine plus S-1 (GS) for metastatic pancreatic cancer (PC) resulted in a high response rate of 44.4%. We have previously conducted a phase I trial of adjuvant GS in patients (pts) with resected PC, and determined a recommended dose of this regimen for the current trial. Methods: Eligibility criteria included macroscopically curative resection of invasive ductal PC and no earlier chemotherapy. The pts received gemcitabine (800 mg/m2/week) intravenously over 30 min on day 1 and S-1 (60 mg/m2/day) orally twice daily from days 1 to 7 every 14 days for 12 cycles. The primary endpoint was overall survival (OS). A total of 55 pts were required based on the assumption of an expected 2-year OS rate of 60% and the threshold rate of 40%, with an α-error of 5% (two-sided) and a β-error of 10%. Results: A total of 55 pts were enrolled between April 2008 and September 2009. The efficacy and toxicity of the treatment were analyzed in 54 pts who had received at least one course of GS therapy. Of the 54, 40 (74%) completed the scheduled 12 cycles, 9 discontinued adjuvant GS within 6 cycles, and the remaining 5 discontinued between 6 and 12 cycles. The reasons for discontinuation were disease progression in 6 and adverse events in the remaining 8. The most common adverse reaction was neutropenia (G3/4: 59.2%, G4: 25.9%). There were no G4 adverse events except neutropenia (1.9%) and hyperkalemia (1.9%). At the time of analysis (median follow-up: 25.4 months), 22 pts were alive without disease, 15 were alive with disease, and the remaining 17 pts were dead. Median OS was not yet reached. The estimated 1-year and 2-year OS rates were 88.9% and 72.1%, respectively. The estimated 1-year and 2-year disease-free survival rates were 57.4% and 44.4%, respectively. Among potential prognostic factors, male gender, head tumor of the pancreas, and the primary tumor smaller than 3 cm were associated with favorable prognosis in a proportional hazard model. Conclusions: Adjuvant GS therapy produced a good disease-free survival (DFS) and OS rates with an acceptable toxicity profile in pts with resected PC. A randomized phase III trial to confirm the efficacy of this regimen is ongoing (JSAP-04).
Nimotuzumab combined with radiotherapy on esophageal cancer: Preliminary study of a phase II clinical trial.
Authors: Liang Jun , Wang Luhua , E Mingyan , Gang Wu , Zhao Lujun , Li Xia , Xiu Xia , Li Ning , Chen Bo , Hui Zhouguang , Lv Jima , Fang Hui , Tang Yu , Bi Nan , Wang Wenqing , Zhai Yirui , Li Tao , Chen Dongfu , Zou Shuangmei , Lu Ning
Published: March 2020

e14511

Background: To evaluate the safety and therapeutic effect of Nimotuzumab (h-R3) in combination with radiotherapy on esophageal cancer. Methods: 42 patients with stage II (Inoperable or refused surgery) to IV (Supraclavicular lymph node metastasis only)were assigned to the phase II clinical trial during Nov. 2008 to Jul. 2010. Histopathological classification of all patients was squamous cell carcinoma. All patients received 50-70 Gy of three-dimensional conformal radiotherapy. 200mg of Nimotuzumab was administered once a week during radiotherapy. Results: There were 9, 25 and 8 patients with stage II, III and IV esophageal cancer, respectively. All patients received 50-70 Gy of radiation therapy except two. 37 patients (88.1%) received Nimotuzumab for more than 5 times. The recorded grade III toxicities (21.4% of all adverse events) included gastrointestinal toxicity, esophagitis, dermatology toxicity and hematological toxicity. Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 0, 22 (52.4%), 17 (40.5%) and 3 (7.1%) patients in one month after treatment. EGFR over-expression rate was 95.2%. Median survival time (MST) was 14 months. One-year and 2-year overall survival (OS) and progression-free survival (PFS) were 54.8%, 36.8% and 39.4, 33.3%, respectively. After a median follow-up time of 17 months, the local recurrence and distant metastases were observed in 18 (42.9%) and 14 (33.3%) patients, respectively. Conclusions: Nimotuzumab combined with radiotherapy were well-tolerated in patients with esophageal cancer. The incidence of grade III toxicity was 21.4%, no grade IV toxicity was observed. EGFR over-expression was found higher than in previous studies. One-year and 2-year OS and PFS were 54.8%, 36.8% and 39.4, 33.3%, respectively. Further study is needed to confirm the therapeutic efficacy of Nimotuzumab in esophageal cancer.
Retrospective analysis of the difference of prognosis between unresectable and recurrent biliary tract cancer: Kansai Hepatobiliary Oncology Group (KHBO) 1001.
Authors: Kanai Masashi , Ikezawa Kenji , Ajiki Tetsuo , Tsukamoto Tadashi , Toyokawa Hideyoshi , Terajima Hiroaki , Furuyama Hiroaki , Nagano Hiroaki , Ikai Iwao , Kuroda Nobukazu , Awane Hiroaki , Ochiai Toshiya , Takemura Shigekazu , Miyamoto Atsushi , Kume Makoto , Ogawa Masao , Takeda Yutaka , Taira Kaoru , Ioka Tatsuya ,   Kansai Hepatobiliary Oncology Group
Published: March 2020

e14518

Background: The difference of prognosis between patients (pts) with unresectable and recurrent biliary tract cancer (BTC) receiving chemotherapy has not been clarified although some studies reported prognostic factors of BTC. In this study, we aimed to compare the prognosis of unresectable BTC with that of recurrent BTC. We also evaluated other prognostic factors of BTC. Methods: This study retrospectively reviewed the data of 403 consecutive pts with pathologically proven unresectable or recurrent BTC who received palliative chemotherapy from 18 hospitals in Japan between April 2006 and March 2009. The 1-year survival rate and overall survival (OS) and patient characteristics were compared between unresectable and recurrent cases. Univariate and multivariate analyses were performed to identify prognostic factors. Results: 380 pts (94.3%) received chemotherapy using gemcitabine and/or S-1. The 1-year survival rate and OS were significantly better in 192 pts with recurrent BTC than 211 pts with unresectable BTC (1-year survival 57.3% vs. 43.1%, p=0.005; OS 398 days [95% confidence interval (CI) 365-430] vs. 323 days [95% CI 282-364], p=0.004). In baseline characteristics, the proportion of pts who had distant metastasis was significantly greater in recurrent BTC than unresectable BTC (77.1% vs. 66.8%, p<0.001). In contrast, lymph node involvement, biliary intervention and elevated tumor marker levels (CEA and CA19-9) were more common in pts with unresectable BTC (p<0.001). After the multivariate analysis, unresectable BTC group still demonstrated a significantly worse survival than recurrent BTC group (hazard ratio [HR] 1.44, 95% CI 1.15-1.80, p=0.002). Other statistically significant prognostic factors were ECOG PS (HR 1.49, 95% CI 1.18-1.87, p<0.001), metastatic disease (HR 1.53, 95% CI 1.20-1.97, p<0.001) and higher CEA (≥5 ng/ml) (HR 1.71, 95% CI 1.36-2.15, p<0.001). Conclusions: The status of unresectable/recurrent disease is identified as one of the prognostic factors for pts with BTC receiving chemotherapy and recommended to be used as a stratification factor in the clinical trials.
Arterial infusion of recombinant human adenoviral p53 gene in treatment of advanced pancreatic cancer.
Authors: Mo Jinggang , He Bing , Tan Kai , Yang Xiaopin , Zhuang Xusheng , Ruan Libin
Published: March 2020

e14523

Background: There are few treatment options for unresectable advanced pancreatic cancer. Here we report beneficial effects of arterial infusion of recombinant human adenoviral p53 gene (rAdp53) in treatment of the late-stage pancreatic cancer. Methods: Sixteen patients having an average age of 56.8 years old, 11 males and 5 females, with unresectable advanced pancreatic cancer were treated using arterial infusion of rAdp53 at dose of 2-4×1012 viral particles (VP) per 3 days for 4 times. The rAdp53diluted into 10 ml ofsaline solution were slowly injected into arterial branches supplying the tumor. Results: Among 16 patients, 56.3% (9/16) achieved a partial response. Overall one year survival rate was 62.5%. Jaundice of 7 in 10 patients was reduced. The ascites of 8 in11 cases was absorbed. General symptoms associated with the late-stage pancreatic cancer were relieved in 81.3% (13/16) of cases. There were no significant side effects or complications observed except for transient fever. Conclusions: The treatment of arterial infusion of rAdp53 showed the beneficiary effects of both safety and efficacy and is a treatment option for unresectable advanced pancreatic cancer.
Occult tumor cells in peritoneal lavage in pancreatic carcinoma patients.
Authors: Srovnal Josef , Benedikova Andrea , Havlik Roman , Klos Dusan , Lovecek Martin , Cahova Dana , Melichar Bohuslav , Hajduch Marian
Published: March 2020

e14556

Background: Pancreatic carcinoma is one of the most aggressive malignancies with a poor prognosis. Assessment of occult tumor cells could prevent aggressive surgery in patients with metastatic spread. The aim of this study was to investigate the prognostic significance of occult tumor cells in peritoneal lavage of patients with pancreatic carcinoma. Methods: This was a prospective study to assess the presence of occult tumor cells in peritoneal lavage of 96 pancreatic carcinoma patients at the time of surgery using real-time RT-PCR for carcinoembryonic antigen (CEA), epidermal growth factor receptor 1 (EGFR1) and human telomerase (hTERT). Gene expression of tested markers was correlated with clinical/pathological characteristics using Kruskal-Wallis Anova and Mann-Whitney tests. Kaplan-Meier methods and Gehan-Wilcoxon tests were used for overall survival analyses. Results: Overall, 65 of 96 (69.9%) pancreatic carcinoma patients died, the overall survival median was 10.3 months. A significant association between CEA expression in peritoneal lavage and the clinical stage was found (p<0.03). In addition, patients with high grade tumors had significantly higher expression of EGFR in peritoneal lavage compared to patients with low grade tumors (p<0.04). The patients with the presence of occult cancer cells detected in the peritoneal lavage using CEA and/or EGFR had significantly shorter overall survival (p<0.001; HR=2.14 [95% CI: 1.30-3.55]) with overall survival median 6.8 months. Conclusions: These data demonstrate that the presence of occult tumor cells in peritoneal lavage is a negative prognostic factor in pancreatic carcinoma patients. Occult tumor cells detection using PCR based methods can identify patients with advanced disease for whom radical surgery is of no benefit. Prospective studies should confirm usefulness of this method for the selection of patients for radical surgery. Acknowledgements: Supported by grants IGA MZ NS 9937‑4, MPOTIP FR-TI1/525, IGA UP LF_2011_018 and CZ.1.05/2.1.00/01.0030.
The prognostic impact of epidermal growth factor receptor (EGFR) in patients with metastatic gastric cancer.
Authors: Werner Dominique , Atmaca Akin , Pauligk Claudia , Steinmetz Kristina , Colak Havva , Altmannsberger Hans-Michael , Jäger Elke , Al-Batran Salah-Eddin
Published: March 2020

e14557

Background: The prognostic role of the epidermal growth factor receptor (EGFR) in metastatic gastric cancer has not been established. Methods: EGFR was analyzed by immunohistochemistry (IHC) in a total of 357 patients (formalin-fixed, paraffin-embedded samples) and by real-time quantitative PCR (RTqPCR) in 130 patients with esophagogastric cancer. Staining intensity on IHC was scored in EGFR 0, 1+, 2+ and 3+. Staining intensity (alternatively intensity x % positive cells or the H-Score) and quantitative mRNA expression were correlated with progression-free (PFS) and overall survival (OS) and pathological and clinical characteristics. Results: On IHC, EGFR was negative, 1+, 2+, and 3+ in 205 (57%), 50 (14%), 62 (17%), and 40 (11%) patients, respectively. EGFR 3+ status correlated positively with intestinal type histology (p=.05) but no other correlations between baseline criteria such as age, sex, ECOG, tumor location, type of metastatic sites, and type of sampling and EGFR status were found. PFS and OS were similar in patients with EGFR-positive vs. those with EGFR negative gastric cancer, regardless whether positivity was defined as ≥1+ (PFS, 5.3 vs. 5.7 months, p=.185; OS, 10.6 vs. 10.9 months, p=.463) or as 3+ (PFS, 5.7 vs. 4.9 months, p=.159; OS, 8.6 vs. 10.8 months, p=.377) or when alternative scores were used such as the H-score. The multivariate overall survival analysis indicated that EGFR status is not an independent prognostic factor (hazard ratio 0.84, 0.56 to 1.12, p=.227). There were also no significant differences in progression-free or overall survival when patients were categorized according to median (PFS p=.173, OS p=.116) or quartile (PFS p=.634, OS p=.767) distribution of EGFR mRNA expression or when the cut-off with the highest predictive value was calculated (PFS p=.148, OS p=.189). Conclusions: EGFR status is not prognostic of patient’s outcome in metastatic gastric cancer.
The role of tumor vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFR) polymorphisms in the prediction of clinical outcome for advanced hepatocellular carcinoma receiving sorafenib.
Authors: Faloppi Luca , Scartozzi Mario , De Minicis Samulele , Svegliati Baroni Gianluca , Bianconi Maristella , Giampieri Riccardo , Maccaroni Elena , Bittoni Alessandro , Del Prete Michela , Mandolesi Alessandra , Loretelli Cristian , Belvederesi Laura , Biagetti Simona , Bearzi Italo , Benedetti Antonio , Cascinu Stefano
Published: March 2020

e14561

Background: Hepatocellular carcinoma (HCC) still represents a medical challenge in cancer therapy. In recent years the introduction of new targeted therapies has radically changed the approach to the disease and patients outcome. Currently the therapeutic stronghold is a TKIs directed against the VEGF family (sorafenib). Polymorphisms of VEGF and its receptor genes are involved in regulating angiogenesis and lymphangiogenesis and thus in growth tumor control. The aim of our study is to evaluate the potential predictive and prognostic role of VEGF and VEGFR polymorphisms in determining the clinical outcome of HCC patients receiving sorafenib. Methods: 38 histologic samples (biopsies and surgical specimens) of HCC patients receiving sorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients time to progression (TTP) and overall survival (OS) were analysed. Results: VEGF-AI rs25648 C>T polymorphism was statistically significant in OS (15.0 months for C vs 9.4 months for T; p=0.025). VEGF-AII rs10434 G>A was statistically significant for TTP (4.1 months for G vs 1.2 months for A; p=0.0076) and OS (14.2 months for G vs 1.7 for A; p<0.0001). VEGF-CII rs7664413 C>T was significant in TTP (13.4 months for C vs 2.0 for T; p=0.0125) and OS (14.7 months for C vs 5.6 for T; p=0.0007). VEGR2-I rs1870377 A>T was significant in TTP (19.9 months for A vs 3.0 for T; p=0.0271) and OS (29.6 months for A vs 11.9 for T; p=0.0096). Conclusions: In our analysis patients with G polymorphism at rs10434, C polymorphism at rs7664413 and A polymorphism at rs1870377 seem to have a better response (PFS and OS) during treatment with sorafenib. Patients with C polymorphism of rs25648 seem to have an advantage only for OS. These polymorphisms of the VEGF-A gene are probably connected with a better control of the neoangiogenesis process during TKIs therapy, maybe leading to vasculature normalization. VEGF-C is a ligand of VEGR2 and seems to have a closely relationship with lymphangiogenesis.
Factors predicting outcome of G1/2 GEP NET after PRRT with Lu177-octreotate.
Authors: Ezziddin Samer , Attassi Mared , Yong-Hing Charlotte Jane , Sabet Amir , Ahmadzadehfar Hojjat , Willinek Winfried , Gruenwald Frank , Guhlke Stefan , Biersack Hans-Juergen
Published: March 2020

e14565

Background: Outcome analyses of G1/2 NEN stage IV after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. This study aims to establish predictors of survival. Methods: Retrospective analysis of 74 consecutive GEP NET patients undergoing PRRT with 177Lu-octreotate. Patients had unresectable metastatic disease and a G1/2 grading (33 pancreatic, 41 non-pancreatic GEP- NET), documented morphologic or clinical progression within < 12 months and/or uncontrolled disease. Response (modified SWOG criteria) was correlated with potential impact factors: origin, function, burden, and uptake of tumor, age, Ki-67-index, Karnofsky score, baseline tumor marker levels. Predictors for survival were analyzed with Kaplan-Meier curves (log-rank test) and multivariate analysis (p<0.05). Results: The response rates were 36.5% PR, 17.6% MR, 35.1% SD, and 10.8% PD for the entire cohort, 54.5% PR, 18.2% MR, 18.2% SD, and 9.1% PD for pancreatic NET, and 22.0% PR, 17.1% MR, 48.8% SD, and 12.2% PD for non-pancreatic GEP-NET. The median progression-free (PFS) and overall (OS) survival was 26 months (95% CI, 18.3 - 33.7) and 55 months (95% CI, 48.8–61.2), respectively. The only factor associated with decreased PFS was a Ki-67 index >10% (p=0.002). For OS, besides the Ki-67 index, a Karnofsky score ≤70% and a baseline NSE of >15 ng/ml independently predicted shorter survival (each p<0.005, HR 3.0 - 3.4). Patients with a Ki-67 index >10% still had a median PFS and OS of 19 and 34 months, respectively. Conclusions: This study confirms the favorable outcome of G1/2 NET after PRRT. Independent predictors of survival are the Ki-67 index, the patient‘s performance status and the baseline NSE level. Nevertheless, patients with a Ki-67 >10% may still benefit from PRRT as demonstrated by the long-term outcome.
Metronomic therapy with 5-FU, weekly nab-paclitaxel, leucovorin, and oxaliplatin, plus bevacizumab for advanced pancreatic cancer: A phase II study.
Authors: Isacoff William H. , Reber Howard A. , Hines Oscar J , Donahue Timothy R. , Purcell Fay M. , Clerkin Barbara M. , Clerkin Kara M.
Published: March 2020

e14582

Background: The objective of this open label phase 2 study was to evaluate low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy for patients with advanced pancreatic cancer. Continuous infusion of 5FU, calcium leucovorin plus paclitaxel and oxaliplatin has been shown to be active in patients with pancreatic cancer. As a protracted low dose infusion, 5FU is anti-angiogenic and has been demonstrated to be synergistic with bevacizumab. Bevacizumab and nab-paclitaxel are synergistic as seen in the treatment of breast cancer. Methods: Since July 2008, we treated 40 patients with 5FU (180mg/m2/day x 14 days) via an ambulatory pump. Calcium leucovorin (20mg/m2) IVP, nab-paclitaxel (100mg/m2) IV as a 30 minute infusion and oxaliplatin (75mg/m2) IV as a 60 minute infusion were given on days 1, 8, and 15. Bevacizumab (5mg/kg) IV over 30 minutes was given on days 1 and 15. Cycles were repeated every 35 days. There were 24 females and 16 males. The median age was 58. 34 patients had stage IV disease. Results: The median overall survival is greater than 17 months. A partial response was observed in 50% of the patients. There were 22 patients with prior treatment, 11 of whom responded to the protocol. 34 patients began treatment with an elevation of their CA19-9 greater than 40. Of these, 26 patients were subsequently noted to have greater than 50% reduction in their CA 19-9; 17 of whom had an objective CT scan response to therapy. Toxicity (grade 3 and 4) included stomatitis, diarrhea, fatigue, nausea, neuropathy, hypertension and renal failure. Hematologic toxicity included anemia, neutropenia and thrombocytopenia. 19 patients stopped treatment due to disease progression, 18 patients stopped due totoxicity. There were no chemotherapy related deaths. Conclusions: This non-gemcitabine based regimen resulted in response rates and survival benefits greater than that which is ususally observed with gemcitabine based therapy. Low dose continuous (metronomic therapy) cytotoxic chemotherapy when combined with anti-angiogenic therapy is safe and effective for patients with advanced pancreatic cancer.
The outcome of peptide receptor radionuclide therapy (PRRT) in North American patients with advanced well-differentiated neuroendocrine tumors (WD-NETs).
Authors: Naraev Boris , Sharma Nancy , Engelman Eric Steven , Bushnell David L , O'Dorisio Thomas M. , Halfdanarson Thorvardur Ragnar
Published: March 2020

e14600

Background: PRRT is frequently used in Europe for patients with advanced WD-NETs, but it is not yet readily available in the USA. We analyzed data on 135 North American patients seen at our institution who underwent PRRT. Methods: Cases were identified by searching the University of Iowa Neuroendocrine Tumors Database. Groups were compared using a Wilcoxon rank-sum test, and survival was calculated with the Kaplan-Meier method. Results: Men were 64%, women 36%; median age at diagnosis was 51 years (18 – 78). The primary tumor originated in the small bowel (SBNET) in 37.8%, pancreas (PNET) 26.0%, lung 13.3%, unknown primary 9.6%, other sites 13.3%. PRRT was performed at the University of Basel, Switzerland in 68.8%, University of Iowa in 25.2%, and elsewhere in 6%. 90Y was used in 83.2% and 177Lu in 15.3% for the first PRRT. Median dose of radiation was 180 mCi (range 7.6 – 360). 116 patients received two treatments with median time between the treatments 2.1 months (range 0.4 – 110). Survival is shown in the table. Radiographic responses (any) at 1-6 months after PRRT were observed in 65.8%, 11.1% had a mixed response, and 15.4% progressed. A biochemical response (>50% reduction in chromogranin A and pancreastatin levels) was seen in 18% and 17.3% respectively but data was frequently missing. Conclusions: North American patients with WD-NETs have a relatively long survival. The OS from 1st PRRT was much less than OS after diagnosis, suggesting that PRRT is used late in the disease course. PRRT appears to be a valuable treatment option for WD-NETs, especially SBNETS, and its role earlier in the disease course warrants investigation. [Table: see text]
Neoadjuvant chemoradiotherapy for potentially resectable esophageal squamous cell carcinoma and the significance of Rad51 expression as a factor predictive of the treatment response.
Authors: Saeki Hiroshi , Nakanoko Tomonori , Ohtsu Hajime , Kawano Hiroyuki , Ando Koji , Oki Eiji , Ohga Takefumi , Morita Masaru , Kakeji Yoshihiro , Toh Yasushi , Maehara Yoshihiko
Published: March 2020

e14601

Background: The clinical significance of neoadjuvant chemoradiotherapy (NACRT) for potentially resectable esophageal squamous cell carcinoma (ESCC) and its effect on the development of postoperative complications are unclear. On the other hand, the Rad51 expression is related to the sensitivity to chemotherapy or radiotherapy; however, the significance of the Rad51 expression in ESCC has not yet been clarified. Methods: 1) One hundred sixty-eight patients with clinical Stage II-III (cStageII-III) ESCC were classified into two groups consisting of 76 who received NACRT followed by esophagectomy and 92 patients who received surgery alone. The prognosis and incidence of postoperative complications were retrospectively compared between the two groups. The pathological response to NACRT as well as the patient prognosis were also analyzed for the NACRT group patients. 2) The expression of Rad51 was investigated in pretreatment biopsy specimens in 41 ESCC cases who underwent surgery after NACRT, and the findings were compared with the pathological response to NACRT. Results: 1) The 5-year survival rate was 47.7% in the surgery alone group and 56.5% in the NACRT group, and the difference was not a statistically significant (p=0.4831). However, the 5-year survival rates of patients in whom NACRT was Grade 3 (markedly effective), was obviously better than that of the other patients (Grade0/1 – ineffective/slightly effective: 36.9%, Grade 2 - moderately effective: 53.8%, Grade 3 - markedly effective: 100%). The incidence of postoperative complications was 31.5% in the surgery alone group and 40.8% in the NACRT group, and the difference was not a statistically significant (p=0.2121). 2) Grade 3 was more frequently observed in Rad51-negative cases (n=13) than Rad51-positive cases (n=28; 71.4% vs. 28.6%, p=0.0239). Conclusions: The pathological complete response of NACRT is critical for improving the survival of patients with cStageII-III ESCC. The Rad51 expression in pretreatment biopsy specimens was therefore suggested to be a useful predictive factor for the response to NACRT.
Phase II study of nimotuzumab combination with paclitaxel and cisplatin as the first-line treatment in patients with local advanced or metastatic esophageal squamous cell cancer (ESCC): An interim analysis.
Authors: Zhang Xiaodong , Lu Ming , Gong Jifang , Gao Jing , Wang Xicheng , Zhang Xiaotian , Li Jie , Li Yan , Li Jian , Zhou Jun , Lu Zhihao , Shen Lin
Published: March 2020

e14604

Background: Nimotuzumab is a genetically engineered humanized antibody (mAb) that recognizes an epitope located in the extracellular domain of human EGFR. Evidences have shown that nimotuzumab is effective and safe in SCCHN. The combination of paclitaxel/cisplatin (TP) is a standard regimen for advanced or metastatic ESCC. This open uncontrolled phase II study was designed to determine the efficacy and safety of nimotuzumab in combination with TP as the first-line treatment in advanced ESCC. Methods: All patients have histology/cytology confirmed advanced or metastatic ESCC with ECOG PS 0-2. The treatment plan is as the following: paclitaxel administered intravenously (IV) 175 mg/m2 on d1 and cisplatin IV 30-35mg/ m2/d on d1-2, every 21 days for 6 cycles, and nimotuzumab IV 200mg weekly. For patients with stable disease (SD) and better, nimotuzumab will be given continuously after 6 cycles of TP. The primary endpoint is objective response rate (RR) with 56 patients enrollment (target RR >60%); secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety/ tolerability. The coordinations between EGFR and ERCC1 with response of treatment will be analyzed. Results: Up to date, 25 patients (male/female, 20/5; median age 58) have been enrolled. All patients were evaluated for toxicity and 22 are evaluable for response. 14 (63.6%) had a confirmed partial response (PR) and 7 (31.8%) had SD as their best responses with disease control rate of 95.4%. Only one patient had progressive disease (PD). Grade 3 or 4 neutropenia, neutropenic fever and anemia occurred in 52.2%, 4% and 13% respectively. Nonhematological toxicities were generally mild with grade 1 or 2 alopecie, hypodynamia, anorexia, nausea, arthralgia, and itch of skin occurring in 80%, 60.9%, 43.5%, 34.8%, 30.4%, and 21.7%. One patient had a grade 3 haematuria. Conclusions: The interim analysis showed that the combination of nimotuzumab with TP is tolerated reasonably well in patients with advanced or metastatic ESCC and encouraging efficacy. The study is ongoing with coordination of biomarkers and response as well.
5-FU/leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) induction followed by chemoXRT in borderline resectable pancreatic cancer.
Authors: Kharofa Jordan , Kelly Tracy R. , Ritch Paul S. , George Ben , Wiebe Lauren Allison , Thomas James P. , Christians Kathleen K. , Evans Douglas B. , Erickson Beth
Published: March 2020

e14613

Background: FOLFIRINOX improves overall survival compared to gemcitabine in patients with metastatic PCa. We retrospectively evaluated the feasibility of using induction FOLFIRINOX followed by chemoXRT to improve resectability in borderline resectable PCa. Methods: All patients with borderline resectable, biopsy-proven PCa treated with the FOLFIRINOX between 1/2009 -11/2011 were reviewed. Borderline resectable PCa was defined by computerized tomography (CT) imaging as tumor-induced SMA abutment of <180 degrees, SMV occlusion, or findings suspicious but not diagnostic for metastatic disease. CT imaging was obtained following induction chemotherapy and after chemoXRT prior to surgery. Results: Twelve patients with borderline resectable disease were treated with FOLFIRINOX induction (median of 4 cycles [range 3-8]). Chemotherapy details are listed in table 1. Tumors in 9 patients had SMA abutment or SMV occlusion and the median pre-treatment CA 19-9 was 297 U/ml (1-3432 U/ml ). Following induction chemotherapy, all patients proceeded to chemoXRT (50.4 Gy [1.8 Gy/fx] with concurrent gemcitabine [n=8] or capecitabine [n=4]). The median CA 19-9 reduction following systemic therapy alone was 58%. One patient did not complete chemoXRT due to infectious and hematologic toxicities. Following all neoadjuvant treatment, 7 (58%) of the 12 patients underwent successful PD. All 7 patients who underwent PD had an RO resection and only one patient had lymph node metastases. The median survival has not been met with median follow up of 13 months. Conclusions: In medically fit patients with borderline resectable PCa, induction FOLFIRINOX followed by chemoXRT is feasible and may facilitate a margin negative resection and histologic response in regional lymph nodes. [Table: see text]
Efficacy of tumor treatment field (TTF) therapy alone and in combination with chemotherapyin pancreatic cancer preclinical models.
Authors: Giladi Moshe , Schneiderman Rosa S. , Porat Yaara , Itzhaki Aviran , Mordechovich Daniel , Weinberg Uri , Palti Yoram
Published: March 2020

e14616

Background: TTF therapy is a novel, non-invasive treatment modality for solid tumors and was recently approved by the FDA for recurrent glioblastoma. It utilizes alternating electric fields to inhibit tumor growth, by mitotic spindle disruption and destruction of plasma membrane integrity during cytokinesis. TTF inhibits the growth of many solid tumor cell lines in vitro and in vivo. The optimal treatment for pancreas cancer remains elusive, thus we sought to evaluate the efficacy of TTF in pre-clinical pancreatic cancer models. Methods: Cultures of hamster and human pancreatic adenocarcinoma cell lines (PC1-0 and AsPC-1, respectively) were treated with TTF (frequencies ranging from 75 to 300 kHz), using two pairs of perpendicularly oriented insulated transducer arrays. Once determining optimal frequency, TTF was combined with chemotherapy (gemcitabine or 5-Fluorouracil, 5-FU). Hamsters bearing syngeneic, orthotopic pancreatic tumors were treated with either TTF alone or in combination with gemcitabine or 5-FU. Results: TTF treatment had significant inhibitory effect on proliferation of pancreatic cancer cultures. The maximal inhibitory effect for PC1-0 and ASPC-1 was observed when TTF frequencies of 100 and 150 kHz were applied (respectively). The application of TTF to cultures treated with either gemcitabine or 5-FU resulted in an additive inhibitory effect. In-vivo, TTF therapy, either alone or in combination with chemotherapy, resulted in a significant decrease in tumor weight and volume. Compared to chemotherapy alone, TTF increased tumor response to both gemcitabine and 5-FU. Histological analysis demonstrated higher mitotic index in TTF-treated tumors, consistent with the mitotic arrest previously shown in TTF treated cultures. Conclusions: TTF therapy demonstrated efficacy in pancreatic adenocarcinoma in both in vitro and in vivo models. These results support the evaluation of this novel treatment modality in combination with standard chemotherapy in pancreatic cancer patients. A pilot study is in development to test the clinical benefit of combined TTF and gemcitabine in patients with advanced pancreatic adenocarcinoma.
Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC).
Authors: Keskin Serkan , Sen Fatma , Aydogan Fatma , Ekenel Meltem , Kilic Leyla , Saglam Sezer , Sakar Burak , Disci Rian , Aykan Faruk
Published: March 2020

e14628

Background: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy naïve AGC patients. Methods: Patients (n=54) with locally inoperable or distant metastasis, and performance status of 0–2 were eligible. The triplet combination chemotherapy consists of docetaxel 60 mg/m2 day 1, cisplatin 60 mg/m2 day 1, 5-flourouracil 600 mg/m2 for 5 days continuous infusion were administered every 21 days, up to 9 cycles. Prophylactic G-CSF was not allowed. Two of the patients treated with second line cisplatin/capecitabine. None of the patients treated with radiotherapy. Results: In all, 36 (67%) patients were male and 18 (33%) were female; median age was 59 years (range: 23-80 years). Majority of patients (n=46, 85%) were metastatic disease and 8 (15%) of them were locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (%43) and 18 (39%) of the 46 cases, respectively. The median cycle of chemotherapy was 6 (ranging from 1 to 9 cycles). In assessing fifty patients for response evaluation, one had complete response. The partial responses achieved in 27 (54%) patients. Seventeen patients (34%) had stable disease and 5 (10%) progressed. Of 2% (n=4) and 11% (n=6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. One patient developed febrile neutropenia. Severe thrombocytopenia, hepatic and renal toxicity were not seen. During median follow-up time (8.1 months, range: 1.3-24), 28 (52%) patients were died. The overall and progression-free survival were 11.6 [95% CI: 10.2-13] and 7.7 [95% CI: 6.8-8.7] months, respectively. Conclusions: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as original DCF in AGC with acceptable and manageable side effects.
Stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma with Child-Pugh class B.
Authors: Cardenes Higinia Rosa , Lasley Foster D , Kwo Paul , Perkins Susan M. , Maluccio Mary A.
Published: March 2020

e14683

Background: Stereotactic body radiotherapy (SBRT) is a promising therapeutic modality in hepatocelular carcinoma (HCC). A Phase I trial was conducted at Indiana University (IU) in patients with Child Pugh Class (CPC) A and B. Based on our results, patients with CPC-B patients with score <=7 continued enrollment in the phase II. We now present an interim analysis for this patient population. Methods: 14 patients with HCC with liver cirrhosis, CPC-B, were treated with SBRT in a Phase I-II trial at IU. All patients were scheduled to receive five fractions, 800 cGy per fraction (total dose 4000 cGy), 1-2 fractions per week. Dose was prescribed to the 80-90% isodose line covering the planning target volume (PTV). A modified RECIST criterion was used to determine local failure. Demographics, clinical variables, treatment –related toxicities within 90 days of end of treatment, and local control (LC) at 6 and 12 months were tabulated. Progression Free Survival (PFS), Time to Progression (TTP), and Overall Survival (OS) estimates were calculated using Kaplan-Meier methodology. This was an unplanned interim analysis. A formal interim analysis will take place later. Results: There were 13 males and 1 female; median age of 56.5 years (range 49-69). All patients had 1 treated lesion. Median (range) for gross tumor volume (GTV) (cc) was 40.1 (8.0-74.6); PTV volume (cc) was 120.1 (34.7-210.0); and uninvolved liver volume (cc) was 2137.9 (973.0-2796.0). There were 3 grade 4 toxicities, 1 each of hyperbilirubinemia, hypokalemia, and thrombycytopenia. Four patients underwent orthotopic liver transplant. Local control at 6 and 12 months were 90% [95% C.I. (55.5%, 99.8%)] and 87.5% [95% C.I. (47.4%, 99.7%)], respectively. Median PFS is 11.0 months (95% CI: 3.9 months, 17.4 months). Ten patients died or progressed including 4 patients who died without progressing. Median TTP is 17.4 months (95% CI: 5.3 months, upper limit not estimable). Median OS is 19.8 months (95% CI: 4.0 months, upper limit not estimable). Conclusions: in carefully selected patients with hepatocellular carcinoma in the context of CPC B liver cirrhosis, score less or equal than 7, SBRT is an effective therapy with a good toxicity profile. Phase II is ongoing.