bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of 18FDG PET and pathological response following neoadjuvant chemotherapy for oesophageal cancer
Authors: Harrison C. , Park R. M. , O’Neill C. , McManus D. , Hughes S. , Carey D. , Kennedy A. , McGuigan J. , McManus K. , Eatock M. 
Published: March 2020

14026 Background: Response to chemoradiation for oesophageal carcinoma on PET scanning is associated with pathological response and survival. Recent trials suggest that neoadjuvant chemotherapy for oesophageal cancer improves disease free and overall survival. We have examined the relationship between PET and histopathological response in those who have undergone surgical resection following preoperative chemotherapy in Northern Ireland. Methods: We assessed 20 consecutive patients with resectable oesophageal cancer. Staging in all patients included an endoscopic ultrasound scan and PET scan before and after preoperative chemotherapy and a PET scan after pre-operative chemotherapy. PET response (≥50% decrease in SUVmax) and pathological response were assessed independently by a Nuclear Medicine specialist and two histopathologists. Evidence of histopathological response was assessed using the Mandard criteria and by determining the proportion of the total blocks of tumour with evidence of viable disease. Results: 20 have been treated, 15 males and 5 females with a median age of 68 (range 39–76). Clinical staging suggested stage III disease in 12 patients (60%), stage IIa in 6 (30%), stage IIb and IVa disease 1 in each group. 16 patients with adenocarcinoma received 3 cycles of ECF chemotherapy and 4 with squamous cell carcinoma received 2 cycles of Cisplatin/5FU chemotherapy. The median time to surgery from first chemotherapy was 101 days (range 84–165). Final pathological stage was less than predicted by pre-treatment staging in 9 patients (45%). PET response was seen in 10 patients (50%), of these, 9 had a Mandard score of ≤3. With median followup of 8 months (range 3–21 months), 18 patients (81.9%) are alive disease free, 3 (13.6%) have died from disease, 1 (4.5%) died postoperatively. Conclusions: In this small series evidence of response to pre-operative chemotherapy assessed by reduction in SUVmax on 18FDG PET scanning is associated with pathological response. We suggest that this association is worthy of further evaluation and prospective investigation. No significant financial relationships to disclose.
Phase II study of S-1 and biweekly docetaxel combination in advanced or recurrent gastric cancer
Authors: Kakeji Y. , Oki E. , Nishida K. , Koga T. , Tokunaga E. , Morita M. , Emi Y. , Maehara Y. 
Published: March 2020

14031 Background: Docetaxel (TXT) and S-1 are active agents against gastric cancer. A synergistic antitumor effect has been shown in a preclinical study (Takahashi et al., Oncology 2005), and our previous phase I trial demonstrated the safety and tolerability of the combination, and its potent activity. To prospectively evaluate toxicity and efficacy of S-1/ biweekly TXT, we conducted the current phase II study in patients with advanced and recurrent gastric cancer. Methods: Patients (pts) with advanced or recurrent gastric cancer, who have not received any chemotherapy except postoperative chemotherapy (not including S-1 or TXT), were eligible for the trial, and were treated with docetaxel 35 mg/m2 one hour iv infusion on day 1 and 15, and S-1 at a full dose of 80 mg/m2/day for two weeks every four weeks. Results: Thirty-five pts with measurable lesions (RECIST) (10 females, 25 males; performance status [PS] 0/1/2: 23/8/4, age 27–74, differentiated/undifferentiated adenocarcinoma: 19/16) have been enrolled. A total of 113 cycles were administered (median 3, range 1–6), and all pts were assessable for toxicity and efficacy. Grade 3–4 toxicities were: neutropenia in 20.0% (grade 4: 11.4%) of patients, leukocytopenia in 11.4% (grade 4: 0%), anemia in 5.7%, appetite loss in 8.6%, stomatitis in 8.6%, fever in 2.9%, and fatigue in 2.9%. All treatment related toxicities resolved, and no toxic death was reported. Thirteen partial responses (PR) were obtained, resulting in an overall response (OR) rate of 37.1% (95% CI: 0.22–0.55). Thirteen pts (37.5%) had stable disease, and 4 pts (12.5%) progressed. The tumor control rate was 74.3% (95% CI: 0.57–0.88). The median survival time (MST) and time to treatment failure (TTF) were 326 and 75 days, respectively. Conclusions: The combination of S-1/ biweekly TXT is active in advanced or recurrent gastric cancer, and can be given safely with proper management of adverse events even in outpatient clinic. S-1/ biweekly TXT is one of the most effective regimen to control metastatic gastric cancer with less toxicity. No significant financial relationships to disclose.
New criteria for complete response (CR) after definitive chemoradiotherapy for recectable squamous cell carcinoma of esophagus
Authors: Takeda A. , Koyama I. , Otani Y. , Sasaki Y. , Dikiya T. 
Published: March 2020

14032 Background: According to a series of clinical trials, definitive chemoradiotherapy for esophageal cancer has become one of the accepted treatment methods even for respectable-stage disease. But preciously outlined CR criteria after definitive chemoradiotherapy has not been established. The purpose of this study is to assess the validity of new criteria for CR of esophageal cancer treated with definitive chemoradiotherapy. Methods: We reviewed 40 patients with T1b-T4, N0–1, M0 (clinical TNM stageI-III) resectable esophageal cancer treated with definitive chemoradiotherapy from April 2000. The patients received 5-Fluorouracil combined with cisplatin plus 50.4–60gy of radiation. We have here designated the CR criteria after definitive chemoradiotherapy 1)able to observe the entire esophagus by endoscopy with disappearance of the tumor lesion and ulceration 2)absence of cancer cells in pathological evaluation 3) no appearance of distant metastasis by CT scan during a series of treatment, in addition 4) no new recurrent lesions at least 6 months using the multimodality observation from determination of primary-CR. Results: Primary CR was achieved in 26 in 40 patients (65%) at the end of a series of treatment. Primary-CR rate in patients with stageI,II,III was 100% (3 out of 3), 85.7% (18 out of 21), 31.2% (5 out of 16) with a remarkable difference between TNM StageI,IIand III patients. There were 6 patients (33.3%) who were confirmed to have local recurrence in stageII esophageal cancer after determination of primary-CR. Likewise, one patient (20%) of recurrent disease in stageIII. Time at first relapse from the initial date of treatment to determine CR was 50–152 days in all recurrent patients. There were no patients with recurrence in the patients who could maintain CR for 6 months over after the determination of CR with a median follow-up of 13 months. Patients maintaining CR after the determination of CR have a significant good survival rate compared with recurrent patients after determination of CR (P<0.001) Conclusions: Our new criteria considered the time from determination of CR appear to be useful for clinical application, predict favorable survival for respectable esophageal cancer patients treated with definitive chemoradiotherapy. No significant financial relationships to disclose.
Efficacy of adjuvant immunochemotherapy with polysaccharide k (PSK) for patients with curatively resected gastric cancer
Authors: Oba K. , Teramukai S. , Kobayashi M. , Matsui T. , Nakazato H. , Ito K. , Sakamoto J. 
Published: March 2020

14038 Background: An anti-tumor effect of non-specific immunomodulators, mainly PSK and OK-432, via an immunological response has been reported and combination immunochemotherapy has been examined. However, the survival benefit of immunochemotherapy for patients with curatively resected gastric cancer was unclear in the world. We performed a meta-analysis in order to evaluate the survival effect of immunochemotherapy employing a biological response modifier Polysaccharide K (PSK) in Japan. Methods: We reassessed by means of meta-analysis of data with central randomization from 5164 patients enrolled in Japanese eight clinical trials. In all eight trials patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoint was 5-year survival odds ratio. Data were analyzed by using a weighted average of the log odds ratios (using Peto’s method). Results: The 5-year odds ratio for all eligible patients was 0.88 (95% confidence interval: 0.78–0.98; p=0.021). There was a significant heterogeneity between the trials (p=0.016). Conclusions: The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve survival of patients with curatively resected gastric cancer. No significant financial relationships to disclose.
PET/CT can direct diagnostic and therapeutic decisions in pancreatic lesions
Authors: Casneuf V. , Delrue L. , Kelles M. , Berrevoet F. , Duyck P. , De Hemptinne B. , Van Damme N. , Monsaert E. , Peeters M. 
Published: March 2020

14048 Background: This study aimed to determine the role of PET/CT in differentiating pancreatic lesions and changing therapeutic approach. Methods: A retrospective analysis of prospectively collected data of 33 PET/CT scans (Philips, Cleveland, USA) was performed. Scans were made between October 2004 and July 2005 for differentiating primary or recurrent pancreatic disease found on CT, MRI or/and EUS. All PET/CT scans were assessed by a radiologist in co-operation with a nuclearist. Pancreatic lesions were interpreted based on visual assessment and by use of a semi-quantitative evaluation (SUV). These results were correlated with pathological diagnoses or clinical follow-up, dividing patients into 2 groups: ‘positive’ (malignant) versus ‘negative’ (benign disease/no lesion). In each patient therapeutic change after PET/CT was assessed. Results: The patient group consisted of 33 consecutive patients, of whom 14 were female. Median age was 61 years (range 33–76 years). SUV values in malignant lesions were significantly higher than those found in benign lesions [5.77 (95%CI 4.08–7.46) versus 1.76 (95%CI 0.79–2.7), P<0.01]. Eleven patients with benign disease or no lesion, had a negative PET/CT. Twenty-two patients had malignant disease of the pancreas. Twenty of 22 patients had a positive PET/CT. Sensitivity and specificity of PET/CT for diagnosing benign or malignant disease visually was 90.9% and 100% respectively. In the benign/no lesion group, a change in therapeutic approach was noted for 9/11 patients (81,8%): no surgery (n=6), no chemotherapy (recurrence excluded, n=3). No change was noted in 2/11 patients (18,2%): no differentiation pancreatitis/tumor. In the malignant group, a change in therapeutic approach was noted for 14/22 patients (63,6%): recurrence confirmed (n=8), up-staged (n=5), down-staged (n=1). No change was seen in 8/22 patients (36,4%): incorrectly sent to surgery (n=4), no differentiation pancreatitis/tumor (n=2), recurrence missed (n=1), false positive diagnosis of liver metastasis (n=1). Conclusions: PET/CT has 90.9% sensitivity and 100% specificity for diagnosing benign or malignant disease visually. PET/CT is a useful tool for directing therapeutic strategy. Overall, therapeutic approach was changed in 23/33 (69,7%) of patients. No significant financial relationships to disclose.
Oxaliplatin plus 5-fluorouracil/folinic acid as palliative treatment for progressive malignant gastrointestinal neuroendocrine carcinomas
Authors: Pape U. , Tiling N. , Bartel C. , Plöckinger U. , Wiedenmann B. 
Published: March 2020

14074 Background: Oxaliplatin in combination with 5-fluorouracil and folinic acid is an antitumoral agent with relatively low toxicity and satisfactory efficacy in several gastrointestinal neoplasms. However, it has not been studied in malignant gastrointestinal neuroendocrine carcinomas (NEC) for which platinum-based chemotherapy is a standard treatment with considerable toxicity. Methods: 16 patients (6 female, 10 male; mean age 57) with documented progress of histologically proven, irresectable, malignant NEC were retrospectively analyzed for safety and efficacy of cytotoxic treatment (from october 2001 to december 2005) according to the FOLFOX-4 regimen. Primary tumors were in the foregut in 9 (2 bronchial, 5 pancreas, 2 stomach), in the midgut in 3 (1 ileum, 2 coecum), and in the hindgut in 2 (1 colon, 1 rectum) patients. The primary tumor was unknown in 2 patients. No patient had clinical signs of hormone hypersecretion. NEC were low-grade malignant in 8 and high grade malignant in the remaining 8 cases. The ki67-index was ≥ 10% in 13 cases (81.3%). Results: A mean of 7.25 cycles (range 1–19) of FOLFOX-4 were administered. Stable disease for a minimum of 9 weeks was observed in 62.5% (10/16) for a mean duration of 19.4 weeks; overall mean time to progression (TTP) as measured by imaging studies was 17.8 weeks (range 2–70 weeks). Reasons for discontinuation of treatment included documented tumor progression in 8 cases (50%) and adverse events in 4 cases (25%) (grade II neurotoxicitiy in 3 cases and grade III neutropenia in 2 cases). 2 patients died during treatment due to tumor progression. 4 patients currently still receive FOLFOX-4 after a mean treatment period of 16 weeks. Side effects according to CTC-NCI-criteria include mild anemia (grade I: n=15), thrombocytopenia (I: n=4, II: n=1), neutropenia (I: n=1, III: n=2), increased serum creatinine (I: n=2), nausea (I: n=4, II: n=4, III: n=1), vomiting (I: n=2, II: n=2), and neurotoxicity (I: n=1, II: n=4). Conclusions: The FOLFOX-4 regimen was well tolerated and effective in progressive malignant NEC with increased proliferative potential. Response may be comparable to current standard regimens. FOLFOX-4 should be evaluated in a prospective controlled clinical trial. No significant financial relationships to disclose.
Levels of circulating endothelial cells (CECs) as early pharmacodynamic markers of activity of anti-angiogenic (AA) therapy in advanced pancreatic cancer (PC)
Authors: Iyer R. V. , Javle M. M. , Pande A. U. , Yu J. , Wilkinson D. , Rustum Y. , Wallace P. 
Published: March 2020

14080 Background: Clinical evaluation of targeted AA therapy may be enhanced by non-invasive biomarkers assessing relevant drug action. In this study we tested the hypothesis that AA therapy with bevacizumab (BV), may result in early release of mature CECs from the tumor vasculature into the peripheral circulation and that this change may serve as a surrogate pharmacodynamic marker of response. Methods: In an ongoing phase II study, patients with advanced PC received BV (15 mg/kg IV, d1), capecitabine (650 mg/m2 twice daily × 14 days) and gemcitabine (1000 mg/m2 IV d1 & 8) given q21 days as first line therapy. CECs (CD34+, CD31+, and CD45− cells) were assessed pre treatment on d1 and on d3 of cycle 1 by 4-color flow cytometry. Quality of life (QOL) was assessed prior to each cycle using the PAN26 questionnaire. Radiographic response by RECIST criteria and CA 19–9 were assessed every 8 weeks. Kendall’s tau, the Wilcoxon signed rank test and Mann-Whitney U-test were used to investigate an association between biomarkers (CEC and CA 19–9), paired data and independent data, respectively. Results: Twenty six of planned 34 pts have been accrued; 13 pts are assessable for change in CECs, 10 are evaluable for response, 3 are too early. Patient demographics: M/F: 4/9; median age 63 years (range 38–79). Best response in 10 pts: 2 PR, 7 SD and 1 PD. On day 3, CECs increased in 8 and decreased in 5 pts compared to baseline. During treatment CA19–9 decreased in 7 and increased in 6 pts. No significant association between CEC and CA 19–9 was detected (Kendall’s tau=-0.2, p=0.367). No significant differences of CEC levels or CA 19–9 were found pre and post-treatment, QOL improved and unimproved, and response and no-response groups. Conclusion: Preliminary analysis in 10 patients reveals no correlation between change in CECs and QOL or radiographic or tumor marker response. This may be due to delayed change (beyond day 3) or release of non-viable CECs that are not currently measured. The limited sample at this early analysis may also account for this finding. These results will be updated as accrual continues with refined CEC measurements which include a viability probe. This study was supported by a grant from NCCN and Genentec pharmaceuticals No significant financial relationships to disclose.
The prognosis of the patients with gastric cancer intraoperatively detected microscopical free abdominal cancer cells at Douglas cavity
Authors: Kishimoto T. , Imamura H. , Furukawa H. , Tatsuta M. , Yamamoto K. , Ohshiro R. , Yonekawa M. , Yamauchi M. 
Published: March 2020

14090 Background: The free abdominal cancer cells in the patients with gastric cancer probably result in peritoneal dissemination. In Japan, the detection of free abdominal cancer cells at Douglas cavity is usually examined immediately after lapalotomy for advanced gastric cancer, because this procedure is recommended in Japanese Classification of Gastric Carcinoma 1999 provided by Japanese Gastric Cancer Association. The patients detected free abdominal cancer cells are diagnosed as stage IV, even if they undergo the surgical curative operation. However some of them have relatively long survival. We investigated that the amount of free abdominal cancer cells or histological type might affect their prognosis. Methods: Surgeon collected 50ml of saline with which Douglas cavity was irrigated. Pathologist stained cells by Papanicolaou follwed by differential centrifugation (2000G for 5 minutes) of saline. Among all 492 patients who underwent surgery for gastric cancer in our institute between 2000 and 2004, 46 patients underwent the curative surgery except free abdominal cancer cells. We investigated the amount of free abdominal cancer cells and histological type as the factors to affect prognosis of these 46 patients. The log-rank test was used to evaluate the survival curves calculated by Kaplan-Maier method. Results: 5 or less and more than 5 cancer cells per 1 cm2 were microscopically detected in 22 (Group A) and 24 patients (Group B), respectively. The median survival time (MST) of Group A and B were 877 and 384 days, respectively (P=0.16). The two-year survival rates of Group A and B are 63.7% and 27.2%, respectively. The cancer cells diagnosed histologically as differentiated and undifferentiated type were detected in 13 (Group X) and 33 patients (Group Y), respectively. The MSTs of Group X and Y were 877 and 383 days, respectively (P=0.13). The two-year survival rates of Group X and Y are 82.1% and 28.9%, respectively. Conclusions: In patients who have advanced gastric cancer with free abdominal cancer cells, a larger number or undifferentiated type of cancer cells may reduce the survival periods of patients with curative resection. No significant financial relationships to disclose.
A phase I study of sequential administration of S-1 and cisplatin (CDDP) for patients with metastatic gastric cancer (MGC)
Authors: Baba E. , Fujishima H. , Kusaba H. , Esaki T. , Ariyama H. , Kato K. , Tanaka R. , Nakano S. , Harada M. 
Published: March 2020

14101 Background: The combination of 5-FU and CDDP has been reported to be active against metastatic gastric cancer (MGC), and great synergy has been shown in vivo and in vitro when 5-FU precedes CDDP. We investigated a sequential combination of S-1 (Tegafur, oxonic acid, CDHP) followed by CDDP for MGC. Methods: In order to determine a maximum tolerated dose (MTD) and recommended phase II dose (RD), we conducted a phase I trial applying increasing doses of oral administration of S-1 (65–80mg/m2) for 21 days and increasing doses of CDDP (60–80mg/m2) on day 22 every 35 days. Pts with metastatic or recurrent gastric cancer, no prior chemotherapy, measurable disease, performance status ECOG less than 3, and adequate organ functions were eligible for the study. Three pts were treated at each dose level with escalation based on toxicity. Fifteen pts were included and evaluated for DLT and MTD. Results: DLT was NCICTC grade 3 anorexia and fatigue in patients treated at the dose level 5 of S-1 80mg/m2 and CDDP 80mg/m2. Other toxicity more than grade 3 was neutropenia (grade 3) and nausea/vomiting (grade 3). Non-hematological toxicities were grade 1/2 and included diarrhea, nausea and stomatitis. There was no treatment-related mortality. The recommended dose was a combination of S-1 80mg/m2 and CDDP 70mg/m2. A tentative median survival was 19.5 months. Conclusions: This sequential S-1 and CDDP administered every 35 days is tolerable and beneficial for patients with MGC, and thus the consequent phase II trial is recommended. A multicenter phase II study is currently under way. No significant financial relationships to disclose.
Escalating doses of hepatic arterial oxaliplatin in combination with docetaxel and capecitabine in patients with liver metastases from non-colorectal gastrointestinal malignancies
Authors: De La Cruz S. , Rodriguez J. , De La Cámara J. , Nagore G. , Viteri S. , Reyna C. , Chopitea A. , Viúdez A. , Gúrpide A. , García-Foncillas J. 
Published: March 2020

14110 Background: Docetaxel (T), oxaliplatin (O) and capecitabine (C) are active agents in gastrointestinal (g.i.) tumors. Synergism has been reported in several preclinical studies. The purpose of this study was to assess the maximum tolerated dose of hepatic arterial oxaliplatin in combination with docetaxel and capecitabine in patients (pts) with hepatic metastases from non-colorectal g.i. tumors. Preliminary evidence of activity was also evaluated. Methods: Patients with liver metastases from gastric (n=3), pancreas (n=6), esophageal (n=2) and cholangiocarcinoma (n=1) were treated with fixed doses of docetaxel (60 mg/m2), capecitabine (650 mg/m2 bid on days 1–14) and escalating doses of hepatic intraarterial oxaliplatin. Oxaliplatin dose was escalated according to the following schedule: level 1, 100 mg/m2; level 2, 110 mg/m2; level 3, 120 mg/m2. The cycle was repeated every 3 weeks. A CT scan or MRI was performed to evaluate response. Liver function tests were performed the day after and before the hepatic arterial infusion. Results: The median number of cycles was 5. At first dose level, 1 pt showed grade 3 mucositis and capecitabine intolerance that required treatment discontinuation. Three pts were later included in the same level with no further toxicity. At dose level 3, grade 3 vomiting was recorded in 1 pt and subsequently this level is now being expanded. Liver function tests on day 2 were elevated over baseline in 10 pts (83%). Seven pts (58%) required morphine due to pain associated with intraarterial infusion. Among 11 evaluable pts, 10 (83%) PRs have been confirmed. Conclusions: Accrual is ongoing at dose level 3. Preliminary data on efficacy seems promising. No significant financial relationships to disclose.