bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of gemcitabine-based chemoradiotherapy (CCRT) after triplet induction chemotherapy (ICT) for locally advanced pancreatic cancer (LAPC): A Taiwan Cooperative Oncology Group (TCOG) study
Authors: Ch’ang H. , Hwang T. , Wang H. , Chang M. , Tien Y. , Chen J. , Hsieh R. , Lin P. , Shan Y. , Cheng A. , Chen L. 
Published: August 2020

e15562 The optimal management of LAPC remains controversial. The efficacy of CCRT is hampered by early systemic dissemination. To treat undetectable metastases and to select patients who are likely to benefit from CCRT, ICT followed by CCRT has recently been extensively evaluated in LAPC. Recently, we showed that triplet chemotherapy consisting of gemcitabine 800 mg/m2 (10 mg/m2/min) followed by oxaliplatin 85 mg/m2 and 48-hour infusion of 5-FU/LV 3,000 and 150 mg/m2 Q 2 weeks, the GOFL regimen, is feasible and active for pts with APC. Chemo-naïve pts with histo- /cytologically proven unresectable LAPC, and bi-dimensionally measurable diseases were eligible. Patients who did not experience disease progression (PD) after 6 cycles of GOFL would had CCRT consisting of weekly gemcitabine 400mg/m2 plus 50.4Gy/28 fractions of radiation 4–6 weeks later. After CCRT, pts were re-evaluated for surgical intervention and those with unresectable disease would continue GOFL until PD, unacceptable toxicity, patient's refusal or death. Among the 50 enrolled pts (24F/26M, median age 58.5 years), 48 had definitively unresectable diseases. After induction GOFL, 16 (32%) pts were off-studied because of PD in 12 (24%) and ICT-related toxicity in 4 (8%, PD/UE group). Among the 34 (68%) with objective response or stable disease after 6 cycles of ICT, 27 (54%) who completed the assigned multimodality treatment are categorized as CCRT group; whiles 7 (14%) who either declined CCRT (in 5) or still on ICT (in 2) are categorized as non-CCRT group. The median PFS and OS for the ITT population were 9.1 and 14.5 months, respectively. The median PFS for PD/UE, non-CCRT and CCRT groups were 2.1, 8.2 and 12.8 months, respectively; whiles the OS were 8.5, 15.0 and 18.3 months, respectively. The most common grade 3–4 toxicities were neutropenia (40%), anemia (14%), infection (16%), nausea (26%), vomiting (20%). Grade 2–3 peripheral neuropathy was observed in 7 of 29 who received post-CCRT GOFL. Conclusion: Three months of triplet ICT followed by gemcitabine-based CCRT is feasible and likely to prolong the survival of selected LAPC pts. Prospective, randomization study is warranted to validate the findings. No significant financial relationships to disclose.
Hepatic arterial infusion chemotherapy using low-dose cisplatin and 5-fluorouracil (5-FU) in the treatment of patients with advanced hepatocellular carcinoma with portal vein tumor thrombus or refractory to transarterial chemoembolization: A single institute outcome analysis
Authors: Nishimura T. , Matsumoto S. , Kanai M. , Ishiguro H. , Kitano T. , Yanagihara K. , Fukushima M. 
Published: August 2020

e15563 Background: Although sorafenib has been reported to prolong survival of patients with advanced hepatocellular carcinoma (HCC), the prognosis of those who did not respond to or are not candidate to transarterial chemoembolization (TACE) remains poor. The aim of this outcome analysis is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted injection port in the treatment of such patients. Methods: From the prospective cohot database of Outpatient Oncology Unit, Kyoto University Hospital, patients with HCC who had been treated with HAIC using low dose cisplatin and 5-FU (cisplatin 10mg and 5-FU 250mg for day 1–5, repeated serially for three or four weeks, then repeated once weekly) between October 2003 and December 2008 were searched for. All adverse events were assessed according to Common Terminology Criteria for Adverse Events v3.0. Survival analysis was performed by using Kaplan-Meier method. Prognostic factors were assessed using Log-rank test. Results: Forty-one patients were identified. The indications of HAIC were: (1) the presence of portal vein tumor thrombus (20/41 cases, 49%), (2) failure to TAE (19/41, 46%) or (3) not candidate for TAE due to the presence of extrahepatic disease (2/41 case, 5%). One complete response and 7 partial responses were observed, overall response rate being 19.5% (95%CI, 7.4–31.6%). Median overall survival was 26.1 month (95%CI: 9.6–45.6). Commonly observed grade 3/4 adverse events were thrombocytopenia (10 cases, 16.3%) and neutropenia (10 cases, 16.3%). There was a trend that fewer death occur in patients who responded to HAIC (1/8 cases, 12.5%) as compared to patients who did not (11/33, 33.3%), but log-rank test failed to detect a statistical significance (P=.145). Conclusions: HAIC for patients with advanced HCC who are not candidate for TACE warrants randomized controlled trial. No significant financial relationships to disclose.
Effect of understaging of early oesophageal tumors on treatment
Authors: Rohatgi A. , Naji S. , Hamouda A. , Ross P. J. , Mason R. C. 
Published: August 2020

e15572 Background: Early and node negative oesophageal cancers do not undergo chemotherapy as it is felt that as the risk of lymph node metastasis is small, early operative intervention is considered the best option. We analysed a prospective database in a tertiary referral centre to see, with current preoperative staging modalities, if a significant number of patients were under staged and hence under treated preoperatively. Methods: Four hundred and fifteen patients underwent esophagectomies for cancer in our unit between March 2000 and December 2006. 117 were preoperatively staged as either T1/T2 N0. Pre-operative staging was by gastroscopy, endoscopic ultrasound (EUS), CT scan and PET-CT. These were discussed in a multi-disciplinary meeting and as per current evidence did not undergo preoperative chemotherapy. Results: 115 patients were analysed as two were excluded. Preoperatively there were 35 T0N0, 30 T1N0, and 50 T2N0. There were 42 (36.5%) patients who were under staged utilising the standard preoperative staging protocol. These were preoperatively staged as T0N0 –2, T1N0 –6, T2N0 –34. 6 did not have EUS, only 4 had a PET- CT and 1 had a staging laparoscopy. Gastroscopy, CT scan and EUS was the staging protocol in 87%. Post op staging was T1N1–7, T2N1–12, T2N2–1, T3N0–10, T3N1–11, T3N2–1. Conclusions: Utilising current preoperative staging methods one third of patients were under staged. Looking specifically at T2N0 68% were under staged. We feel that early oesophageal cancer especially T2N0 disease may benefit from neoadjuvant chemotherapy based on the current staging protocols. No significant financial relationships to disclose.
Changes in cardiopulmonary reserves associated with neoadjuvant therapy in patients with esophageal cancer
Authors: Hofstetter W. L. , Hightower C. E. , Morris G. S. , Sun X. G. , Riedel B. J. , Mehran R. J. , Hearon C. M. 
Published: August 2020

e15589 Background: Recent treatment trends for resectable esophageal cancer have moved toward the addition of neoadjuvant chemoradiotherapy. This additional therapy, however, places these patients at increased risk for loss of physiologic/functional capacity. If present, such declines can delay resection of the primary tumor until the patient has physiologically recovered from this insult. To determine whether physiological reserves decline, peak exercise performance was assessed before and after completing neoadjuvant therapy Methods: In this prospective study seventeen male patients (60.5 + 7.1 years) with esophageal cancers underwent a symptom limited, standard ramp bicycle ergometer cardiopulmonary exercise test (CPET) before and after completing neoadjuvant therapy. The exercise protocol sequentially entailed 3 minutes of quiet resting, 3 minutes of unloaded cycling, ramp protocol to peak exercise tolerance, and 3 minutes of recovery. Ramp rates (5–25 watts/.min) were individually chosen to achieve test durations of 8–12 minutes. Expired gases were measured for volume and gas fractions via breath-by-breath analysis (Medical Graphics CardiO2/CP system). STATISTICAL ANALYSIS: Physiological data were analyzed by paired t-tests (α=0.05). Data are presented as mean + standard deviation. Results: Pre treatment exercise testing occurred immediately before onset of treatment. Post treatment exercise testing typically occurred 45 + 17 days after neoadjuvant ended and 11 + 10 days before surgery. Peak exercise capacity (VO2peak) and anaerobic threshold declined 11.9 % and 10.5 % respectively (p < 0.01) over the neoadjuvant therapy treatment period. Both oxygen pulse (VO2/HR) and pulse pressure product (HR X SP) at VO2peak also significantly declined (p< 0.01) over the treatment period. Conclusions: These results suggest 1) both systemic and peripheral changes contribute to an overall physiological and functional decline in patients undergoing neoadjuvant therapy and 2) efforts aimed at preserving optimal physiological/functional capacity may be warranted during this period. No significant financial relationships to disclose.
Elucidating genetic events in human hepatocellular carcinoma
Authors: Rosario C. , Gladdy R. , Ko M. , Pollett A. , Dennis J. , Swallow C. 
Published: August 2020

e15590 Background: Hepatocellular carcinoma (HCC) is prevalent world wide with increasing incidence in North America. 4q is a commonly deleted region in HCC and is lost in 32% of premalignant cirrhotic nodules but the precise molecular lesion involved in tumor initiation remains unknown. Human Plk4, a member of the polo family of cell cycle regulating serine /threonine kinases is located on 4q28. Plk4 is a haploinsufficient tumor suppressor in mice, with 50% of animals developing spontaneous tumors, most commonly multifocal primary HCC. We hypothesize that Plk4 plays a role in the initiation of human HCC. Our purpose was to determine the levels of Plk4 in human HCC and investigate possible genetic interactions with the tumor suppressor p53. Methods: Formalin-fixed paraffin-embedded sections of human HCCs, adjacent non-neoplastic liver tissue and gallbladder tissue were microdissected. DNA was extracted and manual LOH analysis was performed. To asses Plk4 expression, RNA from the hepatoma cases was used for real time RT-PCR. To elucidate a genetic interaction, Plk4 p53 compound mutant mice were generated and murine embryonic fibroblasts (MEFs) were derived and cultured. Results: In HCC Plk4 LOH rates varied from 57% for the marker closest to Plk4 to 8% for the marker furthest away (n=32). Using an intragenic marker the rate of LOH was 45% (n=24). Studies in CRC (n=46) and pancreas cancer specimens (n=40) showed only background levels of LOH. Expression of Plk4 in HCC tumor samples that displayed LOH at the Plk4 locus was reduced compared to non-neoplastic liver. Plk4±p53−/− mice showed acceleration of tumor formation compared to Plk4+/+p53−/− mice. Plk4±p53−/− MEFs had increased levels multinucleation, centrosome amplification and aneuploidy compared to Plk4+/+p53−/− cells. In addition these cells were tumorigenic in vivo whereas Plk4+/+p53−/− cells were not. Conclusions: Our results demonstrate significant rates of LOH at the Plk4 locus specifically in human HCC and indicate that this is associated with decreased Plk4 expression. In addition, our studies of compound mutant mice suggest a possible genetic interaction of Plk4 and p53 in tumor development. No significant financial relationships to disclose.
Clinical significances of preoperative serum IL-6 and CRP level in operable gastric cancer
Authors: Lee S. , Kim D. , Oh S. , Kwon H. , Jang J. , Kim S. , Kim M. , Kim K. , Han J. , Kim H. 
Published: August 2020

e15591 Background: The interleukin (IL)-6 pathway is one of the mechanisms liking inflammation and angiogenesis to malignancy. As the C-reactive protein (CRP) is representative marker of inflammation, recently CRP has been reported to be associated with processing of disease in many cancers. This study aims to determine the preoperative serum levels of IL-6 and CRP in gastric carcinoma, and correlate them with disease status and prognosis. Methods: A total of 115 patients receiving gastrectomy entered this study. Serum level of IL-6 was measured by using Enzyme-Linked Immuno-Sorbent Assay (ELISA) and CRP was measured by using immunoturbidimetry. Histological findings were included depth of tumor invasion, lymph node (LN) metastasis, and TNM stage (AJCC Stage Groupings The staging systems; Primary tumor, regional LN, metastasis). Results: The more cancer invasion and stage are high, the more preoperative serum IL-6 levels are high. IL-6 level was correlated with depth of invasion (P=0.006) and TNM stage (P<0.001). Preoperative CRP level also correlated with depth of invasion (P<0.001), TNM stage (P=0.001), and presence of peritoneal seeding metastasis (positive 0.66 ± 0.69 mg/dL, negative 0.20 ± 0.29 mg/dL; P<0.001). When we put cutoff value of IL-6 level (6.77 pg/dL) by ROC curve, although patients’ survival did not reach the median value, it shows significant difference in time to progression (TTP; P<0.001) and overall survival (OS; P<0.010). But, CRP did not show significance to patients’ TTP and OS. Conclusions: Preoperative serum IL-6 and CRP levels might be markers of tumor invasion and TNM stage. Preoperative high IL- 6 level was a poor prognostic factor of disease recurrence and overall survival in patients with gastric cancers. No significant financial relationships to disclose.
Cetuximab plus docetaxel-cisplatin (DC) as first-line treatment for locally advanced or metastatic gastric cancer: Preliminary results of a phase II study
Authors: Fahlke J. , Ridwelski K. , Florschuetz A. , Kettner E. , Leithaeuser M. , Kroehning H. , Stuebs P. , Zierau K. , Lippert H. 
Published: August 2020

e15592 Background: Based on promising published data, this multicenter, phase II study was initiated to investigate a combined treatment using DC and cetuximab in the first-line setting for patients with gastric cancer. Methods: Patients aged 18–75 years with stage III (T4, nonresectable) or stage IV gastric cancer, ECOG performance status (PS) ≤2, and life expectancy ≥3 months were recruited to receive cetuximab (400 mg/m2 on day 1 then 250 mg/m2 q1w) and DC (D 75 mg/m2 and C 75 mg/m2; both as 1-h infusions on day 1 and then q3w). Treatment was stopped in the event of disease progression, intolerable toxicity, or consent withdrawal. Tumor staging was performed after cycle 3 and then every 12 weeks. The primary endpoint was overall response rate and secondary endpoints included time to progression, overall survival and toxicity. Planned accrual was 79 patients. A per-protocol interim response analysis was planned for the initial 20 evaluable patients. Results: Preliminary data are available for 30 patients; median age 64 [range: 40–73] years; median ECOG PS 1 [range: 0–2]; adenocarcinoma 87%. Median cycles administered were 3 [range: 1–14] and the median follow-up was 1.63 months. The overall response rate was 27.3% (complete response, n=1; partial response, n=5). Stable disease was observed in 10 patients, and disease progression in 6 patients. The most relevant NCI-CTC grade 3–4 hematologic events per patient were leukopenia and neutropenia (73%), anemia (13%), and febrile neutropenia (10%). Major grade 3–4 nonhematologic toxicities were nausea (30%), vomiting (20%), diarrhea (13%), acne (13%), and fatigue (13%). Conclusions: DC and cetuximab were well tolerated and resulted in promising response rates and a predictable toxicity profile. The study is ongoing. No significant financial relationships to disclose.
Usefulness of PET/CT in the diagnosis of distant metastases of potentially operable gastric adenocarcinoma
Authors: Gallego R. , Fuster D. , Ginés A. , Ortín J. , Ayuso J. R. , Momblan D. , Arguis P. , Conill C. , Pons F. , Maurel J. 
Published: August 2020

e15598 Background: 1) To evaluate the usefulness of Positron Emission Tomography with combined 18F-Fluorodeoxyglucose with Computed Tomography (PET/CT) in the diagnosis of distant metastases in patients with gastric adenocarcinoma (GAC) compared to spiral double contrast thoracoabdominal Computed Tomography (CT); 2) To establish the utility of PET/CT in the detection of peritoneal carcinomatosis compared to laparoscopy. Methods: Thirty prospective patients (22 men, 8 women; mean age 67±11) who underwent endoscopic ultrasound and were classified as T2–3N1 or T3Nx GAC were included in this study. Whole body images were obtained 1 hour after injection of 370 MBq of 18F-Fluorodeoxyglucose. CT was performed within 2 weeks of PET/CT. Laparoscopy was performed without remarkable incidences. All findings were confirmed by histopathology examination and/or by at least 6 months follow- up. Results: Distant metastases were found in 9/30 cases: carcinomatosis (3), retroperitoneal (3) or mediastinal (2) pathological lymph nodes and one case of bone metastases (1). PET/CT diagnosed unsuspected distant metastases by CT in 4/9 patients (retroperitoneal (1) or mediastinal (2) pathological lymph nodes and 1 case of bone metastasis in the spine). In 1/3 patients with histopathological confirmed diagnosis of peritoneal carcinomatosis by laparoscopic findings was negative by PET/CT, and considered as a false negative case. On the other hand, 3 patients with initially positive peritoneal carcinomatosis by invasive laparoscopy were finally diagnosed as benign lesions. These lesions did not show significant uptake in PET/CT and were considered as true negative cases. Conclusions: 1) PET/CT is useful in the diagnosis of distant metastases in patients with GAC 2) Further studies are needed to establish the role of PET/CT to detect peritoneal carcinomatosis. No significant financial relationships to disclose.
Phase II study of irinotecan, 5-fluorouracil (5-FU) and leucovorin combination chemotherapy in taxane and cisplatin-based chemotherapy-refractory metastatic gastric cancer
Authors: Yoon J. , Cho S. , Bae W. , Hwang J. , Shim H. , Chung I. 
Published: August 2020

e15599 Background: The role of the second line chemotherapy in advanced gastric cancer was not clear, but possibility of prolongation of survival is open question. Irinotecan is promising agents in gastric cancer and this phase II study evaluated the efficacy and safety of combination chemotherapy with irinotecan, high dose of 5-fluorouracil (5-FU) and leucovorin in taxane and cisplatin based chemotherapy refractory metastatic gastric cancer. Methods: Eligible criteria were as followed; histologic confirmed adenocarcinoma of stomach, previously treated with taxane and cisplatin, age≥18, Eastern Clinical Oncology Group (ECOG) performance status of 1 or less, adequate organ function. Irinotecan (150 mg/m2) as a 30-min infusion and leucovorin (200 mg/m2) as a 15-min infusion were given on day 1, followed by 5-FU 400 mg/m2bolus infusion then 5-FU 2,400 mg/m2 as a 48-hour continuous infusion. This cycle was repeated every 2 weeks until disease progression or unacceptable toxicities. Results: Thirty-four patients were enrolled. The median age was 57 years (range 27–73 years), and the ECOG performance status of all patients was 1. All patients were evaluable for safety and survival and twenty seven patients (79.4%) were evaluable for tumor response. The overall response rate was 18.5% (95% CI: 3.9–33.1). The median progression free survival and overall survival were 4.6 (95% CI: 2.4–6.9) and 9.3 months (95% CI: 5.2–13.4), respectively. Greater than grade 3 haematological toxicities were neutropenia in nine (26.5%), febrile neutropenia in one (2.9%) and thrombocytopenia in one patient (2.9%). The major non-haematological toxicity was asthenia, but most of patients showed grade 1 or 2. Greater than grade 3 non- haematological toxicities were elevated AST/ALT in four (11.8%), hyperbilirubinemia in two (5.9%), nausea in two patients (5.9%). Conclusions: This results showed that the combination chemotherapy with irinotecan, 5-FU and leucovorin was well tolerated and active in taxane and cisplatin refractory patients. No significant financial relationships to disclose.
Phase II study of S-1 in combination with paclitaxel as a first-line treatment for patients with advanced/recurrent gastric cancer
Authors: Toh U. , Yamana H. , Koufuji K. , Mine T. , Aoyagi K. , Miyagi M. , Imaizumi T. , Shirouzu K. 
Published: August 2020

e15615 Background: Taxanes and S-1 have been shown to be effective in patients with advanced gastric cancer and they have a considerable single-agent activity, respectively. We evaluated the combination of paclitaxel and S-1 as first-line chemotherapy for advanced or recurrent gastric cancer (AGC). Methods: All patients with histologically confirmed AGC with unresectable or metastatic diseases, measurable lesions, PS 0–2, age between 18 and 75, and no contraindication to chemotherapy were eligible in this study. Prior adjuvant chemotherapy finished at least 6 months before enrollment was allowed. Treatment included S-1 80 mg/m2 p.o. twice daily on days 1–14 and paclitaxel 60 mg/m2 i.v. on day 1, 8, 15 with a 2-week interval until disease progression or unacceptable toxicities. Results: Between MAY 2004 and Match 2008, total 20 pts were enrolled in this study. The median age was 56.5 years (range, 38–73). Nine pts had recurrent disease after previous curative gastrectomy and 8 had previous adjuvant chemotherapy. After a median 4 (range, 1–9) cycles of chemotherapy, 12 pts were evaluable for toxicity and 20 pts for response. In intention-to-treat analysis, the overall response rate was 62.9% (95% C.I., 36.2–69.6%), including 0 CR, 6 PRs, 8 SDs, and 6 PDs. After a median follow-up of 8.6 months (range, 0.9–17.9), median time to progression was 6.3 months (95% C.I., 3.6–6.9) and median overall survival was 11.6 months (95% C.I., 8.5–20.7). Commonly observed grade 3/4 adverse events were neutropenia (40% of patients), anemia (10%). There was no neutropenic fever or treatment-related death. Conclusions: The combination of paclitaxel and S-1 appear to have well efficacy, manageable toxicity and is well tolerated in patients with AGC. Further studies of this combination should be considered. No significant financial relationships to disclose.