bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of FOLFOX4 in patients with hypoalbuminemia or immune impairment
Authors: Shibata M. , Yumiko N. , Hirano T. , Matsuo S. , Abe H. , Yajima Y.
Published: August 2020

e15141

Background: The effects of chemotherapeutic agents are understood to be regulated by many factors including tumor factors such as sensitivity to drugs and host factors. Among these host factors, nutritional conditions and immune function of cancer-bearing host has been told to relate the effects of chemotherapy, however, it has not been clarified yet. Methods: We have analysed the relationships between the effects of FOLFOX4 and nutritional markers such as serum albumin concentrations and immunology markers including counts of lymphocytes and neutrophils, the ratios of these counts G/L: granulocytes/lymphocytes) and serum concentrations of immunosuppressive acidic protein (IAP) in the patients with disseminated colorectal cancer who have received FOLFOX4. All these blood examinations were performed before the first administration of FOLFOX4 as a first line chemotherapy in 18 patients with disseminated colorectal cancer. Results: Firstly serum albumin levels have shown significant correlation to lymphocyte counts and did inverse correlation to neutrophil counts and G/L ratios. The albumin levels in the patients with PD of FOLFOX outcome was significantly lower than in the patients with PR(p<0.05) and SD (p<0.05). The lymphocytes counts in the patients with PD were significantly lower than in those with PR (p<0.05) and SD (p<0.05). Neutrophil counts, on the other hand, was significantly higher in the patients with PD than in those with PR (p<0.01) and SD (p<0.05). IAP, have been recognized as a marker of immune-suppression in patients with cancer was higher in the patients with PD. Conclusions: Thus the nutritional status is closely related to the immune status in patients with cancer, and the markers of these conditions may present important informations in prediction of results of cancer chemotherapy.

No significant financial relationships to disclose.
A qualitative analysis of a focus group discussion on patient decision making in cancer care
Authors: Srinivasaiah N. , Joseph B. , Gunn J. , Hartley J. , Monson J.
Published: August 2020

e15145

Background: Patient preferences should play an important role when decision making in cancer care. Literature is increasingly demonstrating that surgeons and physicians have divergent preferences for treatment options compared with their patients and with each other. Cancer psychology is an important aspect of cancer care. Qualitative research is a gateway to explore this. We aim to explore opinions and thoughts among surgical colleagues about “patient decision making in cancer care”. Methods: A pilot focus group discussion among members of the academic surgical unit involving 4 consultants, 3 registrars and 3 research fellows. The discussion was audio-taped and transcribed. Qualitative methodology was adopted for analysis. Thematic analysis using framework approach was done thereby identifying Themes & Outcomes. Results: Themes that emerged are Evidence based clinical practice, Knowledge, Decision making, Patient Information, Risk, Communication, Consent, Socioeconomic factors and Patient empowerment, Outcomes derived are to increase the evidence base, Increase the clinician and patient knowledge, provide adequate information, Decisions to be based on patients best interest, Communicate risk in a understandable manner, Take patients views, knowledge and demands into consideration, Conclusions: Patient decision making in cancer care is slowly evolving, where decisions are not only made taking into account patients views, knowledge and demand but are also driven by them in a minority. Time is a factor and in years to come the patients will play an increased role in their treatments taking into account tradeoffs and risks between survival and quality of life.

No significant financial relationships to disclose.
Capecitabine combined with oxaliplatin (XELOX) as first-line chemotherapy in colorectal cancer with liver metastases
Authors: Mahfouf H. , Djeddi H. , Belhadef S. , Bouzid K. , Bentabak K.
Published: August 2020

e15146

Background: The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated. Methods: Chemotherapy-naive patients confirmed histologic colorectal cancer with liver metastases, adequate born morrow, renal and hepatic function, measurable diseases were considered eligible for the study. Treatment: Six cycles of oxaliplatin 85 mg/m2 day1 plus capecitabine 1250 mg/m2 twice daily days 1–14 every 21 days Results: Twenty six patients were evaluated for safety and efficacy (male/female, 12/14). Median age was 53 years (range 32–75 years). A total of 142 cycles have been administered: median per patient 4 (range 3–6 courses). In an intent-to-treat efficacy analysis, One complete and ten partial responses were achieved [overall objective response rate (ORR): 42, 3%; whereas 7 patients had stable disease and eight patients had progressive disease. Seven patients from 11 with objective response underwent major liver resection: 2 bisegmentectomy, 1 left lobectomy, 4 segmentectomy, and receive the same regimen of chemotherapy (Six cycles) as an adjuvant treatment and still alive without recurrence. The overall survival (OS) was 19, 2 months. The median response duration was 7 months. The median time to progression (TTP) was 8 months. The grade 3 toxicities were diarrhea (7%), fatigue (4%), neurotoxicity (2%), neutropenia (2%), and thrombocytopenia 4%). Conclusions: The combination of oxaliplatin and capecitabine is safe and has a promising activity in patients with liver metastatic colorectal carcinoma.

No significant financial relationships to disclose.
Usefulness and faults of the sentinel lymph node biopsy using dye technique in distal gastrectomy for gastric cancer
Authors: Rino Y. , Yukawa N. , Murakami H. , Masuda M. , Oshima T. , Sato T. , Yamamoto N. , Imada T.
Published: August 2020

e15509

Background: We apply sentinel node biopsy (SNB) in distal gastrectomy to perform it as safe limited surgery. Limited surgery is a procedure in which the extent of lesion resection and lymph node dissection is reduced. We assessed usefulness and faults of intraoperative diagnosis of lymph node metastasis in this regard. Methods: Surgical procedures: Patent blue (1%) is injected submucosally into 4 to 5 different sites at 1 mL per site around the primary tumor. If blue nodes are found, biopsy and diagnosis of metastasis are performed at this point. Subjects and methods: The study was conducted in 96 gastric cancer patients with a preoperative diagnosis of T1 or mp invasion. Informed consent was obtained from the all patients. There were 65 males and 31 females with a mean age of 64.2 years. Tumor invasion of m, sm, mp, ss, and se was identified in 44, 38, 8, 2, and 4 patients, respectively. All patients underwent open distal gastrectomy (DG) (n=31) or laparoscopy-assisted distal gastrectomy (LADG) (n=65) and Billroth-I reconstruction. Results: The mean number of BNs dissected was 4.5 and 3.7 in DG and LADG cases, respectively. Intraoperative identification and biopsy of BNs could be performed in 34 of 35 DG patients and in 58 of 61 LADG patients. Of the 34 patients in whom BNs were identified, 5 had metastases in BNs confirmed by intraoperative frozen section diagnosis in DG cases. On the other hand, of the 58 LADG patients in whom BNs were identified, 5 had metastases in BNs confirmed by intraoperative frozen section diagnosis in LADG case. False-negative rate was 1.9%. Conclusions: SNB can be performed in LADG as well as in DG. For the case that shows infiltration up to MP, the possibility of lymph node metastasis for other lymph node is considered to be negligible. In obese cases we had some cases of no BNs and false-negative. In consequence, as long as the infiltration is lower than MP, and confirmed that metastasis was not found by blue node biopsy, distal gastrectomy using limited surgery would be thought to be done safely.

No significant financial relationships to disclose.
Plasma IL-6 level and survival of pancreatic cancer patients treated with a VEGFR inhibitor, vatalanib (PTK/ZK)
Authors: Baker A. F. , Dragovich T. , Cui A. , Laheru D. , Campen C. , Von Hoff D. D. , Hidalgo M.
Published: August 2020

e15514

Background: Use of anti-angiogenesis drugs in pancreatic cancer has not yet resulted in significant clinical improvements and it is unknown if there are subsets of patients with pancreatic cancer that may benefit from this therapeutic approach. We have reported on a phase II trial of PTK/ZK (VEGFR inhibitor) in patients (n=65) who have failed or progressed on gemcitabine. The 6- month OS met the primary endpoint of 29 % and there were 2 partial responses. We investigated some of the plasma proteins relevant for angiogenesis in correlation with clinical outcomes on this trial. Methods: Plasma samples were obtained prior to and after 4 weeks of therapy with PTK/ZK, aliquoted and frozen until assayed. Patient plasma was assayed for: VEGFA, VEGFC, VEGFR1, VEGFR2, FGFb, PDGFBB, OPN, ANG2, IL-6, and sIL-6R (SearchLight, Pierce Biotechnology Multiplex ELISA and IL-6 and sIL-6R using R&D Systems).The Spearmen correlation was utilized to look for correlations and changes from baseline compared to post-treatment levels. The correlation of baseline levels with survival were analyzed using the Cox proportional hazard model. Results: Thirty eight paired patient samples were assayed. A significant correlation of baseline values was found between VEGF-C and VEGFR1 (p=0.0496), VEGF-C and VEGF (0.0092), PDGFB and ANG2 (p=0.0003), IL-6 and ANG2 (p=0.0089), and FGFb and OPN (p=0.0281). A correlation in post-treatment change was observed between VEGF-C and PDGFB (p=0.0008), FGFb and OPN (p=0.0374), PDGFB and ANG2 (p=0.0005), IL-6 and ANG-2 (p=0.0464), and VEGF and IL-6 (p=0.0546). Lower baseline IL-6 levels correlated with longer survival (p=0.0227). A post-treatment decrease in plasma IL-6 levels was significantly associated with improvement in survival (p=0.0457). IL-6 mediates multiple effects including angiogenic and pro-survival signaling and has been proposed as a potential prognostic factor in different malignancies. Conclusions: Of all angiogenesis markers analyzed only a post-treatment decrease in plasma IL-6 correlated with improved survival on study. IL-6 warrants further investigation as a potential marker of sensitivity to anti-angiogenesis therapy, especially in patients with pancreatic cancer. Supported by: 1P50 CA95060; 1PO1CA109552–01A1

[Table: see text]
Gender disparities in hepatocellular cancer survival
Authors: Hendifar A. E. , Yang D. , Iqbal S. , Lenz H. , El-Khoueiry A.
Published: August 2020

e15517

Background: Recent reports suggest that estrogen mediated inhibition of IL-6 protects against the development of HCC and may explain the decreased risk of liver cancer in women. We investigated the relation-hip between gender, age, and survival for patients with localized HCC. Methods: We identified 11,097 patients with localized, histologically defined HCC, from 1988- 2003, using the Surveillance, Epidemiology, and End Results (SEER) registry. Age at diagnosis, sex, ethnicity, and overall survival were evaluated using Cox proportional hazards model. The models were adjusted for treatment modality, tumor differentiation, tumor size, lymph node involvement, and number of lesions; they were stratified by year of diagnosis and SEER registry site. Results: 8,111 (73%) patients were men and 2,986 (27%) were women. In univariate and multivariate analyses, female gender, young age (< 55 yo), and Asian ethnicity were all associated with improved overall survival (p<0.001). In patients less than 55 yo, women had a superior OS and cancer specific survival (CSS) when compared to men (OS: 18 months vs. 9, CSS: 31 months vs. 14, p<0.001). Conversely, in patients older than 55, there were no gender differences (OS: 8 months vs. 8, CSS 13 months vs. 11, p = 0.08). Local therapies, including, ablation (HR = 0.47 [0.43–0.53]), hepatectomy (HR = 0.40 [0.36–0.44]), radiation (HR = 0.67 [0.57–0.78]) and transplantation (HR = 0.17 [0.15–0.20]) were also associated with improved survival. There were no interactions identified between gender and treatment use. Conclusions: To our knowledge, this is the first report to highlight the superior outcome of premenopausal women with HCC compared to men. We postulate a potential role for estrogen in influencing the biology of HCC and the response to treatment. These observations are consistent with ones made in other gastrointestinal cancers and with reported preclinical data suggesting a protective role for estrogen. Further studies that confirm these observations and elucidate the biology of estrogen's influence on HCC are needed.

[Table: see text]

No significant financial relationships to disclose.
Prognostic significance of endoluminal ultrasound defined tumor volume (EDTV) in patients diagnosed with esophageal cancer
Authors: Escofet X. , Twine C. , Roberts A. , Dave B. , Rawlinson C. , Chan D. , Crosby T. , Robinson M. , Lewis W.
Published: August 2020

e15519

Background: The aim of this study was to assess the prognostic significance of endoluminal ultrasound defined tumour volume (EDTV) in patients diagnosed with esophageal cancer. The hypothesis was that tumour volume is a better predictor of outcome than tumour length. Methods: One hundred and seventy-four consecutive patients (median age 64y, 128 m) underwent both CT and specialist EUS, and the maximum potential tumour cylinder volume (EDTV) was calculated using the formula πr2L (cylinder volume), where r = tumour thickness (cm) and L = total length of disease, including the position and level of both the primary tumour and proximal and distal lymph nodes (cm). All patients received stage directed multidisciplinary treatment [surgery 104 patients (80 neoadjuvant chemotherapy), definitive chemoradiotherapy 54 patients, and palliative therapy alone 16 patients]. The primary measure of outcome was survival. Results: Survival was related to EUS T (p=0.013), EUS N (p=0.001), EUS M1a stage (p=0.004), EUS disease length (p=0.001), and EDTV (all patients <25cm3, p=0.001, surgical patients <40cm3, p=0.036). Forward conditional multivariate analysis revealed 3 factors to be associated with survival; EUS N stage (HR= 1.646, 95% CI 1.041 to 2.602, p=0.033), EUS M1a stage (HR= 2.702, 95% CI 1.069 to 6.830, p=0.036), and EDTV (HR= 2.702, 95% CI 1.069 to 6.830, p=0.025). Conclusions: EDTV emerged as a new and important prognostic indicator for patients diagnosed with esophageal cancer.

No significant financial relationships to disclose.
Clinical outcome of sequential chemotherapy in metastatic and/or recurrent gastric cancer
Authors: Moon Y. , Rha S. , Jeung H. , Shin S. , Yoo N. , Roh J. , Noh S. , Chung H.
Published: August 2020

e15521

Background: Little is known about data on subsequent chemotherapy (CTx) following 1st-line CTx in stage IV gastric cancer. The purpose of this study was to analyze the natural history of stage IV gastric cancer with sequential CTx Methods: A total of 532 patients (pts) with unresectable gastric adenocarcinoma were studied. They were managed with a strategy of maximal administration of CTx only if pts’ general conditions were allowed. Response evaluation was performed by RECIST every 2 cycles. Response of unmeasurable lesions was dichotomized only into stable disease or progressive disease. Results: When pts were divided into CTx group (460 of 532, 87%) and best supportive care group (BSC; 72 of 532, 13%) resulting from poor performance/pt's refusal/comorbidity (31/23/18), the former had younger age (p = 0.046), better performance (p < 0.001), and less advanced metastatic sites (p = 0.001) than the latter. Median overall survivals from diagnosis of unresectable cancer were 12.0/13.3/2.5 months for overall/CTx/BSC, respectively. 87%/47%/23% of the whole pts received 1st/2nd/3rd-line CTx, respectively. Median number of regimens delivered was 2. Maximally 5th-line CTx was given to 15 pts (3%). Response and disease control rates were 21.7%/12.5%/11.8% and 79.4%/56.3%/49.4% for 1st/2nd/3rd lines, respectively. Median progression-free and overall survivals from CTx were 5.5/3.4/2.5 months and 12.1/7.9/5.5 months for 1st/2nd/3rd lines, respectively. The most common cause of discontinuation of CTx was disease progression (68%/74%/70%) followed by pt's refusal (22%/13%/12%) for 1st/2nd/3rd lines, respectively. Prognosticators were performance status, histology, metastatic site, and CTx before 1st or 2nd line. Conclusions: When pts with unresectable gastric cancer were managed with a strategy of maximal administration of CTx, a considerable number of pts could receive 2nd or 3rd line CTx, showing modest activity. Performance status and metastatic site were consistent prognosticators even if lines changed. Our data on the natural history of stage IV gastric cancer with sequential CTx may suggest that clinical trials can be performed in a 2nd or 3rd line setting as well.

No significant financial relationships to disclose.
A phase II trial of oral S-1 combined with gemcitabine in patients with unresectable biliary tract cancer
Authors: Nakamura K. , Yamaguchi T. , Sudo K. , Hara T. , Denda T. , Azemoto R. , Ishihara T. , Tsuyuguchi T.
Published: August 2020

e15527

Background: Optimal chemotherapy for unresectable biliary tract cancer is yet to be defined. We have conducted the phase II trial of Gemcitabine (GEM) with S-1, oral fluorouracil prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydropridine and potassium oxonate to evaluate the activity and toxicity of such combination in patients with unresectable biliary tract cancer. Methods: Eligibility criteria were pathologically-proven biliary tract cancer, appropriate performance status 0 to 2, age 20 to 79 years, adequate hematological, renal and liver functions, no prior chemotherapy, and written informed consent. S-1 was given orally (30mg/m2) bid for 14 consecutive days and GEM (1000mg/m2) was given on day 8 and 15. Cycle was repeated every 21 days. Results: 30 patients with unresectable biliary tract cancer (Gall-bladder: intrahepatic bile ducts: extrahepatic bile ducts=7:16:7) were enrolled from March 2007 to December 2008. Patients characteristics were: median age; 67 (46–79), male/female; 20/10, PS 0/1/2; 16/13/1. Median number of cycles was 8 (range 1 to 14). Out of total 26 evaluable patients, objective responses were observed in 9 patients (30%); 16 patients achieved stable disease and 1 patients showed disease progression. Median survival was 390 days (95% c.i.: 290 - 490 days). The grade 3–4 toxicities observed were leucopenia (20%), neutropenia (40%), anemia (17%), thrombocytopenia (37%), anorexia (7%), fever (10%), rash (7%) and interstitial pneumonia (7%). Conclusions: The combination chemotherapy with GEM and S-1 was well tolerated and high response rate has been observed. This result is very promising but survival benefit against GEM monotherapy should be demonstrated in future phase 3 studies.

No significant financial relationships to disclose.
Prognostic implication of the maximum standardized uptake value (mSUV) on 18F FDG-PET in patients with metastatic hepatocellular carcinoma
Authors: Shin D. , Han S. , Oh D. , Im S. , Kim T. , Bang Y.
Published: August 2020

e15531

Background: The role of 18F-fluorodeoxyglucose-positron emission tomography (18F FDG- PET) in hepatocelluar carcinoma (HCC) has not been firmly established. We conduct this study to investigate the value of mSUV on 18F FDG-PET as a prognostic factor in HCC, especially in metastatic setting. Methods: We consecutively enrolled HCC patients with extrahepatic metastatic lesions, who have been evaluated with 18F FDG-PET before palliative anticancer treatment, between January 2000 and June 2008 at the Seoul National University Hospital. We retrospectively analyzed the clinical outcome and the value of mSUV as a prognostic factor. Results: A total of 57 patients (male, 86.0%) were enrolled. Median age was 57 years (range, 36–78). Hepatitis B was the predominant cause of HCC (82.5%), followed by non-viral hepatitis (14.0%) and hepatitis C (3.5%). Most patients (94.7%) were Child-Pugh A and 3 patients (5.3%) were Child-Pugh B. The most commonly involved site was lung (47%), bone (26%), and LN (33%). Median serum AFP level was 68ng/ml (range, 2–48000) and the median mSUV was 4.1 (range, 0.5–57.0). Forty patients (70.2%) received systemic chemotherapy, 14 patients (24.6%) received palliative radiotherapy, 23 patients (40.4%) received palliative surgery, and 7 patients (12.3%) received TACE. In univariate analysis of overall survival (OS), patients with mSUV over 4.0, AFP over 400ng/ml, and presence of intrahepatic viable lesion, and no palliative surgery showed significantly shorter OS (p=0.007, p=0.006, p<0.001, p=0.02, respectively). In multivariate analysis of OS, mSUV over 4.0, AFP over 400ng/ml, and presence of intrahepatic viable lesion were independent prognostic factors (p=0.01, p=0.01, p<0.001, respectively). In patients with mSUV > VS <4.0 or AFP > VS <400ng/ml, there was no difference of palliative anticancer treatment pattern. When combined mSUV with AFP, the OS of patients with mSUV >4.0 and AFP>400ng/ml VS mSUV <4.0 or AFP<400ng/ml VS mSUV <4.0 and AFP<400ng/ml was 11.0 months vs 16.0 months vs 35.7 months, respectively (p=0.006). Conclusions: The mSUV on 18F FDG-PET is a prognostic factor for OS in patients with metastatic HCC. The combined analysis of mSUV with AFP can have a more potent prognostic impact.

No significant financial relationships to disclose.
A phase II trial of thalidomide plus tegafur/uracil for patients with advanced/metastatic hepatocellular carcinoma (HCC): Final report
Authors: Hsu C. , Lin Z. , Lee K. , Yeh K. , Hsiao C. , Shen Y. , Chang D. , Wang S. , Hsu C. , Cheng A.
Published: August 2020

e15533

Background: Thalidomide (T) is an anti-angiogenic agent with modest activity in advanced/metastatic HCC. Tegafur/uracil (UFT) is an oral prodrug of 5-fluorouracil with activity against various gastrointestinal cancers. Metronomic chemotherapy has been shown to have anti-angiogenic and anti-cancer effect in preclinical and clinical models. This study evaluated the efficacy and safety of the combination of T and metronomic UFT as first-line therapy for advanced HCC. Methods: Patients (Pts) with advanced HCC not treatable by surgery or other loco-regional therapies received T 100mg bid and UFT 125mg/m2 (based on tegafur) bid continuously. Treatment was continued in the absence of disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) by RECIST; secondary endpoints were disease control rate (CR+PR+SD), progression-free survival (PFS), overall survival (OS), and safety. Results: Between Jul 2006 and Jul 2008, 43 intent-to-treat pts (M/F 41/2, median age 55) were enrolled. Baseline characteristics were HBsAg(+)/anti-HCV(+)/both(+) /both(-) 31/6/1/7; AJCC stage II/III/IV 2/18/23; BCLC stage B/C 1/42; CLIP score ≤3/4 27/16; portal vein thrombosis 65%; extrahepatic metastasis 58%; prior local treatment 72%. There were 4 PR (9.3%) and 10 SD (23.3%), with a disease control rate of 32.6%. Median OS was 4.6 (95% CI, 3.5–7.3) months and median PFS was 1.9 (95% CI, 1.8–2.6) months. The OS and PFS for pts with CLIP score ≤3 were 7.6 and 2.6 months, respectively. Grade 3 leucopenia developed in 1 (2.3%) pt. The most common treatment-related grade 3 non-hematologic toxicities were somnolence (n=4, 9.3%), GI bleeding (n=3, 7.0%), and elevated transaminase (n=2, 4.7%). No grade 4 toxicities occurred. Conclusions: The combination of T with metronomic UFT is a well-tolerated regimen with moderate activity for advanced HCC, and worth further exploration in pts with CLIP score ≤3.

[Table: see text]
Clinical role of regulatory T cell in intraductal papillary mucinous neoplasms
Authors: Morine Y. , Shimada M. , Imura S. , Uchiyama H. , Uchiyama H. , Kanemura H. , Arakawa Y. , Hanaoka J. , Sugimoto K.
Published: August 2020

e15537

Background: Intraductal papillary mucinous neoplasms of pancreas (IPMNs) have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. Recently, several investigators have reported that regulatory T cells (Foxp3+CD4+ T cells including CD4+CD25+ T cells and CD4+CD25- T cells) play important roles in anti-tumor immunity. We previously reported clinical role of increased populations of Foxp3+CD4+ T cells (Treg) in peripheral blood from advanced pancreatic cancer patients (Pancreas 2006). This study was conducted to clarify the clinical role of Treg for surveillance of IPMNs. Methods: Thirty-five patients with IPMNs (IPMC: n=8, IPMB: n=2, IPMA: n=5) and pancreas cancer (n=20) who underwent surgical resection were included in this study. Peripheral blood was withdrawn from IPMN patients (IPMC: n=5, IPMA: n=2) and PC patients (n=20), as well as healthy volunteer donors (n=20) as controls. The peripheral blood mononuclear cells (PBMCs) were subjected to FACScan analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Immunohistochemical expression of Foxp3 (abcam: FOXP3 antibody, 236A/E7), Fascin (Dako: Fascin antibody, 55K-2) and TGF-β (Santa Cruz: TGF-β1 antibody, SC146) in main tumor was assessed in all IPMN patients. Results: The Treg population among the PBMCs was significantly increased in IPMC patients (median: 4.50%) and PC patients (median: 3.06%) compared with healthy donors (median: 1.30%). No significant difference in the Treg population among the PBMCs was observed between IPMC and PC patients. On the other hand, in IPMA patients (n=2), the Treg population among the PBMCs was equivarent to healthy donors (2.40 and 1.85% respectively). In immnohistochemical staining, the positive expression of Foxp3 was 87.5% (7 of 8) in IPMC patients, while in IPMA and IPMB patients, the expression of Foxp3 was not observed. The expression of Fascin and TGF-β was not correlated to malignant potential of IPMNs Conclusions: Increase of Foxp3+CD4+ T cells in the PBMCs is a new promising marker for malignant potential in IPMNs patients.

No significant financial relationships to disclose.
Phase I study of SIR-sphere plus sorafenib as first-line treatment in patients with nonresectable hepatocellular carcinoma: The Asia-Pacific Hepatocellular Carcinoma Trials Group protocol 05 (AHCC05)
Authors: Chow P. K. , Poon D. , Choo S. , Lai H. , Goh A. , Lim T. , Lo R. , Tay K. , Tan S. B. , Soo K.
Published: August 2020

e15538

Background: Sorafenib has been shown to significantly prolong survival in patients with nonresectable hepatocellular carcinoma (HCC) without however significant tumour regression. The addition of radio-ablative therapy could confer additional survival benefit. This phase I trial was carried out to ascertain the toxicities and safety of this combination and was designed as a prelude to a phase II trial. Methods: Eligible patients were administered SIR-sphere (max dose 3 GBq) and subsequently given Sorafenib therapy (400mg bd) either 14 days (Cohort 1: first 3 patients) or 11 days (Cohort 2: subsequent patients) later. Assessment was carried out for 30 days after commencement of Sorafenib. Results: 10 patients were recruited into this phase I trial. The second patient became ineligible for sorafenib therapy after SIR-sphere due to pulmonary bleeding not related to radio-therapy and was excluded from assessment. The characteristics of the patients are in the Table. At the end of the study period, there was no adverse events (AE) of grade 3 or 4 for Cohort 1 and 3 for Cohort 2. The only serious adverse event (SAE) recorded was from Cohort 2. Conclusions: Starting sorafenib 14 days after SIR-sphere therapy is associated fewer AEs and SAEs. The phase II trial has commenced withsorafenib starting 14 days after SIR-sphere. [Table: see text]

[Table: see text]
Phase II trial of biweekly reduced-dose combination chemotherapy of oxaliplatin/5-fluorouracil/folic acid (Modified FOLFOX) as first-line chemotherapy in elderly patients with metastatic or recurrent gastric cancer
Authors: Kim H. , Lee B. , Kim T. , Nam S. , Kim B.
Published: August 2020

e15544

Background: Although combination chemotherapy as ECF (epirubicin, cisplatin, and 5-FU) and DCF (docetaxel, cisplatin, and 5-FU) are effective advanced gastric cancer, but it is too toxic to apply for elderly patients with increased comorbidity. Combination of oxaliplatin and 5-FU has proven to be a effective and tolerable regimen in advanced gastric cancer, and we investigated the efficacy and safety of reduced-dose combination chemotherapy of oxaliplatin/5-FU/folic acid as first-line chemotherapy in elderly patients with metastatic or recurrent gastric cancer. Methods: Elderly patients (≥60 years) with measurable, metastatic or recurrent gastric cancer were enrolled. Patients received oxaliplatin 75mg/m2 (2-hour intravenous infusion on D1), 5-FU 1000mg/m2 (12-hour continuous infusion on D1,2), and folic acid 20mg/m2 (15-minute infusion on D1,2) every 2 weeks. Results: Total 37 patients were enrolled between April 2004 and August 2008. Median age was 67 years old (range, 60 to 80 years), and 22 patients (59.5%) had increased Charlson comorbidity index score (CCI ≥1). Of 36 evaluable patients, 2 patients achieved complete response (CR), and 12 patients partial response (PR) with representing overall response rate of 44.4% (95% CI 27.7- 60.2). Stable disease (SD) was observed in 12 patients (33.3%), and progressive disease in 8 patients (22.3%). The median time to progression was 4.6 months, and median overall survival was 9.2 months. Relative dose intensity was 97.4% in both oxaliplatin and 5-FU. Grade 3 or 4 hematologic toxicities included neutropenia in one patients (2.7%), and anemia in three patients (8.1%). Peripheral neuropathy occurred (grade 2) was only observed in three patients (8.1%). Conclusions: The reduced-dose combination chemotherapy of oxaliplatin/5-FU/folic acid was effective and tolerable in elderly patients with metastatic or recurrent gastric cancer as first-line treatment.

No significant financial relationships to disclose.
Phase II study of mFOLFOX-4 followed by mFOLFIRI in advanced gastric cancer
Authors: Kwon H. , Lee S. , Oh S. , Kim S. , Kim H.
Published: August 2020

e15546

Background: FOLFOX followed by FOLFIRI regimen has been commonly used in colorectal cancer. This combination has also been evaluated in a number of phase II studies in the first- and second-line treatment setting of advanced gastric cancer. We have evaluated the efficacy and toxicity of modified FOLFOX-4 followed by modified FOLFIRI regimens in advanced gastric cancer patients. Methods: Previously untreated patients with advanced or recurrent gastric cancer were enrolled. As first-line therapy, patients received modified FOLFOX-4, bolus ldLV 50mg followed by a 5-FU bolus 400mg/m2 and 22-hour infusion 600mg/m2 on day 1 and 2, with oxaliplatin 85mg/m2 on day 1 every 14 days. At progression, patients received modified FOLFIRI, bolus ldLV 50mg followed by a 5-FU bolus 400mg/m2 and 22-hour infusion 600mg/m2 on day 1 and 2, with irinotecan 150mg/m2 on day 1 every 14 days as second-line therapy. Results: Fifty-six patients were enrolled in first-line mFOLFOX-4. Of these, 32 (57.1%) patients received sequential mFOLFIRI as second-line chemotherapy. In first- line therapy, mFOLFOX-4 achieved 41.4% (95% CI, 28–54%) partial response and 32.1% (95% CI, 20–45%) stable disease. The median time to progression was 4.2 months (95% CI, 2.8–5.5 months). In second-line therapy, mFOLFIRI achieved 18.8% (95% CI, 4–33%) partial response and 31.3% (95% CI, 14–48%) stable disease. The median time to progression was 3.1 months (95% CI, 1.4–4.7 months). Median survival was 12.8 months (95% CI, 9.5–16.0 months) in overall 56 patients, and median survival of sequential chemotherapy was 13.2 months (95% CI, 9.4–16.9 months) in 32 patients. In first-line mFOLFOX-4, NCI-CTC grade 3/4 hematological toxicities were neutropenia and thrombocytopenia in 28 (7.6%), 1 (0.3%) of the cycles, respectively and neutropenic fever was observed in 7 cycles (1.9%). Grade 1/2 sensory neuropathy was observed in three patients (5.6%). In second-line mFOLFIRI, NCI-CTC grade 3/4 hematological toxicity was neutropenia in 20 (19.8%) of the cycles, and neutropenic fever was observed in 5 cycles (4.6%). Grade 3 diarrhea was observed in one patient (3.1%). Conclusions: As sequential chemotherapy, the mFOLFOX-4 followed by mFOLFIRI regimen is both feasible and safe for advanced gastric cancer patients.

No significant financial relationships to disclose.
A novel model including CXCR4 and CDK6 as potential predictive marker for docetaxel (doc) sensitivity in gastric cancer (GC)
Authors: Wei J. , Xie L. , Qian X. , Chen G. , Yu L. , Ding Y. , Liu B.
Published: August 2020

e15548

Background: A growing body of evidence has shed light on biomarkers for chemotherapeutic agent sensitivity in gastric cancer (GC) treatment. It has been demonstrated β-tubulin Ш (TUBB3) and microtubule associated protein tau (MAPT) might be considered as potential markers for taxanes treatment. However, an integrated predictive model for docetaxel (doc) sensitivity is still needed to customized chemotherapy in gastric cancer. Methods: Doc resistant gastric cancer cell line was established by exposure to gradually increasing doc concentration on an intermittent dosage schedule. Microarray was performed to explore different gene expression levels between parental cells and resistant cells. 11 gastrointestinal cancer cell lines were used to validate gene levels by real-time quantitative PCR as well as doc cytotoxicity. Histoculture drug response assay (HDRA) was adopted to examine doc sensitivity in 25 surgically dissected GC specimens. Discrimination analyses were used to determine which linear combinations of these genes best distinguished responder patients from nonresponder patients by adding one more genes each time. Results: After functional analysis of microarray, a panel of 11 genes were further validated, which resulting 4 genes, CXCR4 (P=0.047), CDK6 (P=0.014), USP15 (P<0.001) and CDH1 (P=0.001) that correlated to the doc sensitivity. The mRNA levels of CXCR4 and CDK6 were significantly higher in resistant GC specimens (P=0.0298, 0.022 respectively). A final response index including 5 genes (CXCR4, CDK6, USP15, TUBB3 and MAPT) showed potential predictive value for doc associated chemotherapy with an accuracy of 84% (P=0.001). Conclusions: A predictive model with five genes for doc therapy was generated and showed novel predictive role in doc sensitivity in GC.

No significant financial relationships to disclose.
Neoadjuvant therapy of gastric cancer with cetuximab added to both irinotecan and cisplatin, followed by surgical resection and adjuvant chemoradiation
Authors: Ma H. Y. , Newman E. , Ryan T. , Miller G. , Sarpel U. , Pachter H. L. , Cohen D. J. , Choi H. , Goldberg J. D. , Hochster H. S.
Published: August 2020

e15552

Background: We previously demonstrated the efficacy of irinotecan (CPT) and cisplatin (Cis) combination therapy as neoadjuvant therapy for locally advanced gastric cancer [Newman E et al. J Gastrointest Surg. 2002.]. This trial was designed to add cetuximab (C) to both induction treatment and adjuvant chemoradiation (CRT) with bolus 5-FU/LV. Methods: Pts with untreated locally advanced (T3, T4 or N+) gastric/GE cancers were eligible. Neoadjuvant therapy consisted of Cis 25mg/m2 + CPT 75mg/m2 on d1,8 q21d x 4, C 400mg/m2 on d1, then 250mg/m2 qwk. Curative (R0) resection was performed 4–6 wks later. Adjuvant CRT with 5-FU/LV (425/20/m2 qd x 5 on wks 1,14,19; 400/20/m2 qd x 4 on wk 5, x 3 on wk 9) was given with C 250mg/m2 qwk. Results: Since 11/05, 21 pts [median age 59 (32–82); 9 Caucasian, 11 Asian, 1 Hispanic; 15 male, 20 PS 0–1] received neoadjuvant therapy. The most common toxicities were gr 3 neutropenia (38%), gr 2 rash (33%), gr 2 fatigue (29%); gr 4 included 1 pt each of diarrhea, neutropenia, & hypomagnesemia. 3 did not complete neoadjuvant therapy, due to gr 3 rash, diarrhea and GI bleeding (2 had gastrectomy; 1 lost to f/u). All 18 pts who completed neoadjuvant therapy were surgically explored. 4 had occult metastases, and went off study. 14 underwent R0 gastrectomy (see table); 8 were downstaged, 2 had stable disease, 4 were upstaged compared to the preoperative EUS. There was no postoperative mortality. Of 14 resected pts, 2 did not receive adjuvant therapy (prolonged postoperative recovery), 1 too early to assess, and 11 remaining receiving CRT. The most common toxicities for CRT were gr 3 nausea, gr 3 emesis, gr 2 and 3 fatigue, 3 pts each and 1 each of gr 4 neutropenia and thrombocytopenia. Among the 18 pts who completed neoadjuvant therapy, 5 died of disease, 1 is alive with disease, 12 remain NED with median f/u of 11.6mos (4.1–27.7mos). Conclusions: The addition of C to CPT/Cis as neoadjuvant therapy and to postoperative adjuvant CRT is well tolerated. The regimen induces a favorable pathologic response on the primary tumor. Ongoing evaluation includes K-ras mutation status on outcome and survival benefit. [Supported in part by a grant from BMS.]

[Table: see text]
HER2 status in 146 gastroesophageal carcinomas assessed by two rabbit monoclonal antibodies (SP3 and 4B5) and two in situ hybridisation methods (FISH and SISH)
Authors: Boers J. E. , Meeuwissen H. , Methorst N.
Published: August 2020

e15555

Background: In the industrialized world, the incidence of adenocarcinomas of the distal esophagus/gastric cardia is increasing rapidly and though the incidence of carcinomas of the gastric body / antrum are decreasing they still represent a significant health problem. Several reports claim a significant HER2-positivity in gastro-esophageal adenocarcinomas. A large phase III trial in which HER2-positive gastric cancer patients are treated with trastuzumab is ongoing. New HER2 assessment methods are gaining popularity in breast cancer. Methods: HER2 status was examined in gastro-esophageal carcinomas, comparing SP3 (Labvision) and 4B5 (Ventana) immunohistochemistry (IHC), conventional dual probe HER2 FISH (DAKO), and SISH (Ventana) in a single Dutch institution. Results: IHC was carried out on biopsies of 146 patients with adenocarcinomas of the esophagus (n=44), gastric cardia (n=28), body (n=24) and antrum (n=50). IHC positivity, as defined by an immunoscore 2+ or 3+ using a modified scoring system, was present in 17 cases with the SP3 antibody, and in 24 cases with 4B5. FISH/SISH showed identical results in 40 cases carried out when any immunoreactivity in either antibody was detected. 100% of SP3-IHC-positive cases, and 92% of 4B5-IHC-positive were amplified. The negative predictive value of SP3 and 4B5 (immunoscores 0/1+) was 77% and 95%, respectively. Heterogenous HER2- positivity with partial staining/amplification was present in 73% of the adenocarcinomas, occasionally with only a tumor area of 10–20% showing positivity. HER2-amplification was present in 27% of esophageal and 18% in gastric cardia carcinomas (resulting in 24% amplification of tumors of the esophago-gastric region). In the distal stomach, 7% HER2-amplification was seen. Conclusions: HER2 amplification is present in a significant proportion of esophago-gastric region adenocarcinomas (24%) but at a much lower rate in the distal stomach (7%). Both antibodies can be used for initial screening for possible amplification though the 4B5 antibody has the highest negative predictive value. FISH and SISH yield identical results but the SISH assay offers rapid assessment.

[Table: see text]
Phase II feasibility study of adjuvant S-1 plus docetaxel for stage III gastric cancer patients after curative D2 gastrectomy (OGSG 0604)
Authors: Fujitani K. , Tamura S. , Kimura Y. , Tsuji T. , Matsuyama J. , Iijima S. , Imamura H. , Kurokawa Y. , Tsujinaka T. , Furukawa H.
Published: August 2020

e15567

Background: Although an adjuvant chemotherapy with S-1 has become the standard treatment for stage II-III gastric cancer (GC) patients (pts) after curative D2 gastrectomy in Japan, the survival benefit for stage III pts obtained by S-1 is considered to be modest. S-1 plus docetaxel has shown a good response rate of 56% with prolonged median overall survival (OS) of 14.3 months in pts with advanced GC. This phase II study evaluated the feasibility and safety of adjuvant S-1 plus docetaxel for stage III GC pts after R0 resection. Methods: Patients with curatively resected pathological stage III GC receiving D2 dissection, age 20–80 years, performance status < 1, no prior adjuvant treatment, adequate organ function, and informed consent were given S-1 (80 mg/m2/day) orally for consecutive 2 weeks plus docetaxel (40 mg/m2) intravenously on day 1, repeated every 3 weeks. The treatment was started within 45 days after gastrectomy, and repeated for 4 cycles, followed by S-1 monotherapy until 1 year after surgery. Study endpoints included feasibility of the 4 cycles of S-1 plus docetaxel as primary, and safety, progression free survival (PFS), and OS as secondary. Sample size was set to be 50, which was determined to reject the feasibility of 50% under the expectation of 75% with power of 90% and two-sided α of 5%. Results: Fifty-three pts, 42 males and 11 females with a median age of 65 years, were enrolled between 5/2007 and 8/2008. Pathological stages included IIIA in 36 pts and IIIB in 17 pts. Planned 4 cycles of treatment were delivered to 41 out of 53 pts, with the feasibility of 77.4% (95% CI 63.8–87.7%, P<0.001). Reasons for discontinuation were recurrent cancer in 1 pt, adverse events in 10, and miscellaneous in 1, respectively. Grade 4 neutropenia was observed in 28% of pts with grade 3 febrile neutropenia in 9%. Non-hematological toxicities of grade 3 or more involved fatigue in 6%, anorexia in 9%, and nausea in 6%. No treatment-related deaths occurred. Conclusions: Adjuvant S-1 plus docetaxel was well-tolerated and showed good compliance. Although follow-up is ongoing on survival, this regimen could be a candidate of future phase III trial seeking for the optimal adjuvant chemotherapy for stage III GC pts after curative D2 gastrectomy.

No significant financial relationships to disclose.
A randomized phase III trial to determine the efficacy of postoperative antimicrobial prophylaxis in gastric cancer surgery (OGSG0501)
Authors: Inoue K. , Imamura H. , Kimura Y. , Fujitani K. , Miyake Y. , Matuyama J. , Tatsumi M. , Shimokawa T. , Kurokawa Y. , Furukawa H.
Published: August 2020

e15576

Background: In Japan, antimicrobial prophylaxis (AMP) is typically administered for 3 to 4 days postoperatively in gastric cancer surgery. This far exceeds the recommended 24h or less laid out by the Centers for Disease Control (CDC) guidelines for the prevention of surgical-site infections, after a clean-contaminated operation. Methods: A multicenter randomized phase III trial was designed to evaluate the effect of postoperative AMP in gastric cancer surgery. Patients (pts) were required to have histologically proven gastric cancer which was curable by distal gastrectomy, be classifiable as ASA 1 or 2, and have adequate organ function. Pts were randomized to: (A) perioperative AMP (cefazolin 1g, at <30min before incision, every 3h intraoperative supplements) plus postoperative AMP (cefazolin 1g, twice daily for 2 postoperative days) or (B) perioperative AMP alone. Pts were stratified by institution and ASA. The primary endpoint was the incidence of surgical site infection (SSI). With 171 pts per arm, this study had 80% power to demonstrate non-inferiority with 5% margin of peri-AMP alone and 0.05 1-sided alpha. Results: 355 patients were recruited (A: 179, B: 176) in 7 centers between June 2005 and December 2007. The surgical-site infection rate was 9.0 percent (16 of 178) for peri-/post AMP and 4.5 percent (8 of 176) for peri-AMP alone, with no significant differences (Fisher's exact test: P=0.14, RR=1.98 [95%CI, 0.89–4.44]), but showing a significant non-inferiority (P<0.001). The remote site infection rate was 3.4 percent (6 of 178) for peri-/post AMP and 5.1 percent (9 of 175) for peri-AMP alone, with no significant differences (P=0.44, RR=0.66 [95%CI, 0.25- 1.70]). Conclusions: This multicenter randomized phase III trial confirms that postoperative AMP is unnecessary in patients undergoing distal gastrectomy for gastric cancer.

No significant financial relationships to disclose.
Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG 0506
Authors: Ishii H. , Furuse J. , Boku N. , Okusaka T. , Ikeda M. , Ohkawa S. , Fukutomi A. , Hamamoto Y. , Nakamura K. , Fukuda H.
Published: August 2020

e15578

Background: Fluorouracil (5-FU) chemoradiotherapy has been accepted as standard care for locally advanced pancreatic cancer (LAPC); however, it has not been shown to be superior to chemotherapy alone in gemcitabine (Gem) era. The present multicenter phase II study was conducted to evaluate the efficacy and the safety for the screening of Gem monotherapy against LAPC. Methods: Eligibility criteria included the following: patients (pts) with histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma, pts with UICC clinical stage III (T4N0–1 and M0), all lesions are assumed to be included in the radiation field of 15 cm square, age 20 or older, no prior treatment for LAPC, ECOG performance status of 0, 1 or 2, and adequate organ function. Gem was given intravenously at a dose of 1,000 mg/m2 over 30 minutes on days 1, 8 and 15, repeated every 4 weeks until disease progression. The primary endpoint was %1-year overall survival. A sample size of 50 was required with one-sided alpha of 0.20, beta of 0.10, expected %1-year survival of 40% and threshold %1-year survival of 25%. Results: Between Jan. 06 and Feb. 07, 50 pts from 14 institutions were registered. Patient characteristics were: median age; 67.5 (45–80), male/female; 35/15, PS 0/1/2; 30/20/0, pancreatic head/body-tail; 26/24. The major grade 3–4 adverse events were neutropenia (62%), leucopenia (32%), thrombocytopenia (18%), fatigue (12%), infection-biliary tree (10%), anorexia (8%), and nausea (6%). Hematological toxicity was mostly transient and there was no episode of infection with grade 3–4 neutropenia. There were no treatment-related deaths during the study. Serum CA 19–9 level was reduced by >50% in 37.5% of 40 pts with baseline CA19–9 >100U/ml. Up to the final follow-up in Apr. 08, the median overall survival was 1.25 years (95% CI, 1.06–1.71 years) with a %1-year survival of 64.8% (95% CI, 49.6–76.4%), and the null hypothesis (%1-y survival=25%) was rejected (p<0.0001). Conclusions: Gem monotherapy demonstrated far better survival than historical data of 5-FU chemoradiotherapy in LAPC pts with mild toxicities. In future randomized trial, we will select Gem chemotherapy as a referential arm to compare with the chemoradiotherapy regimen which is under phase II evaluation for LAPC.

No significant financial relationships to disclose.