bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of adjuvant hyperthermic intraperitoneal chemotherapy with three drugs for the prophylactic treatment of carcinomatosis after resection of advanced gastric cancer
Authors: Murata S. , Naito H. , Yamamoto H. , Mekata E. , Shimizu T. , Shiomi H. , Naka S. , Abe H. , Kurumi Y. , Tani T. 
Published: August 2020

e15588 Background: This prospective study was performed to assess the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) with three drugs in patients with curative resection of T3 or T4 advanced gastric cancer. Methods: Patients with curative resection of clinically T3 or T4 advanced gastric cancer were required to be under 75 years of age and to have adequate organ function. After the curative resection of gastric cancer with D2 lymph node dissection and the reconstruction of the alimentary tract, HIPEC was carried out for 30 minutes with 50mg of CDDP, 10mg of MMC, and 1000mg of 5-FU in 5 L saline maintained at 42–43°C. Patients were given an adjuvant S-1 treatment after surgery. Primary endpoint of this study was overall survival. Results: A total of 29 patients were eligible. Pathologically, 8 patients had sub-serosal invasion (pT2(ss)), 18 patients had serosal invasion (pT3), and 3 patients had adjacent organ invasion (pT4). These patients included pT2(ss)pN0 (n=2), pT2(ss)pN1 (n=6), pT3pN0 (n=4), pT3pN1 (n=9), pT3pN2 (n=5), pT4pN0 (n=1), and pT4pN1 (n=2). Median follow-up period was 44 months (10–72 months). Overall 5- year survival rate in all eligible patients was 89.5%. Overall 5-year survival rate in patients with pT2(ss), pT3, or pT4 was 100%, 82.4%, or 100%, respectively. Three patients with pT3 had recurrence of pleural dissemination (n=1), lymph node metastases (n=1), or pulmonary metastases and peritoneal dissemination (n=1). A total of 7 patients had postoperative complications such as continuous pancreatic juice secretion (13.8%), abdominal abscess (10.3%), leakage of the anastomosis (3.4%), and pulmonary insufficiency (10.3%). Conclusions: The present study suggests that HIPEC with three drugs after curative resection of advanced gastric primary cancer is associated with improved overall survival with an acceptable morbidity. No significant financial relationships to disclose.
Second-line pemetrexed–oxaliplatin combination for advanced pancreatic adenocarcinoma
Authors: Mazzer M. , Zanon E. , Foltran L. , De Pauli F. , Cardellino G. , Iaiza E. , Ermacora P. , Aprile G. , Fasola G. 
Published: August 2020

e15597 Background: Few regimens showed efficacy in advanced pancreatic cancer patients (pts) who had failed a first-line gemcitabine-based therapy. However, there is growing evidence suggesting that second-line treatment may provide further disease control in selected pts. Both pemetrexed and oxaliplatin demonstrated activity in this setting, and their combination resulted safe and tolerable.Methods: Pancreatic cancer pts with advanced disease, PS>60, age>18 years, who progressed after a gemcitabine-based therapy were enrolled in a phase II trial, and treated with pemetrexed 500 mg/mq followed by oxaliplatin 120 mg/mq, day 1 every 3 weeks, together with adequate oral folinic acid and intramuscular vitamin B12 supplementation. Accordingly to the Simon Minimax two-stage study design, an accrual of 31 patients was planned, with a minimum response rate considered of interest of 25%, α level 0.10 and β level 0.10. Results: To date, 16 patients have been treated. Of them, 12 progressed during or shortly after gemcitabine (13) or gemcitabine-cisplatin combination (3), with a median time to progression of 186 days. 62 cycles were delivered, with a median of 4 cycles per patient (range 2–8). Overall, the regimen was well tolerated: most common adverse events were mild-to-moderate sensory neurotoxicity and gastrointestinal disturbances. We reported grade 3 anemia, grade 3 thrombocytopenia, and grade 3 fatigue in 1 patient each. Three among the treated patients died within 30 days from last delivered cycle due to progressive disease. Confirmed partial (3) or minor responses (6) were observed in 9 out of 15 evaluable pts, with a median decrease in the Ca 19.9 value of 43% among those who responded. Median progression-free survival was 99 days. At the time of analysis, 3 out of 16 patients are still on treatment.Conclusions: The preliminary results suggest that second-line pemetrexed-oxaliplatin combination is well tolerated and reasonably active, and allow the continuation of the study until the full sample of 31 pts. No significant financial relationships to disclose.
A pilot phase I/II study of combination chemotherapy with nafamostat mesilate and gemcitabine for unresectable pancreatic cancer
Authors: Uwagawa T. , Misawa T. , Iida T. , Matsumoto M. , Gocho T. , Hirohara S. , Sadaoka S. , Yanaga K. 
Published: August 2020

e15600 Background: To improve chemoresistance of gemcitabine (GEM) caused by GEM-induced nuclear factor kappa B (NF- κB) activation, we have conducted combination chemotherapy of GEM with NF-κB inhibitor, nafamostat mesilate (NAM) which is commercially approved as an effective therapeutic agent for disseminated intravascular coagulation, systemic response syndrome, or pancreatitis in Japan for patients with unresectable pancreatic cancer patients through phase 1/2 study. Methods: Study treatment consists of GEM 1,000 mg/m2 on d 8, 15 and 22 plus NAM 2.4∼4.8 mg/kg on d 8, 15 and 22. NAM was administered intra-arterially by continuous regional infusion for 24 hours via an infusion port system one hour before administration of GEM. Overall survival, response rate (RECIST), serum CA19–9 and clinical benefit response (body weight, pain alleviation) were assessed. Results: Between Feb 2007 and Oct 2008, 20 patients with unresectable pancreatic cancer were included in this study. Pts characteristics: male/female: 18/2, median age 63.5 (range 38–79) yrs, median Karnofsky PS 80% (range 70–90%), stage III/IV: 8/12, serum CA19–9 4,662 U/ml (range 88–32,100), baseline visual analogue scale 0–1/2–4/5–7/8–10; 9/4/7/0, baseline analgesic consumption (morphine-equivalent, mg/day) 0/10–100/100>; 10/7/3. The combination of NAM with GEM is well tolerated and MTD has not been reached. The recommended dose was GEM 1,000 mg/m2; NAM 4.8 mg/kg. Overall survival was 8.0 (range 4.7–17) months. CR/PR/NC/PD/not evaluated; 0/3/14/2/1. Serum CA19–9 reduction rate; 89%. Three pts. could become off and 1pt. could reduce oral morphine sulfate, and 5 pts. gained weight. Conclusions: The GEM/NAM regimen is safe, and the clinical data, including overall survival and clinical benefit response, suggest that the initial clinical outcome of this trial has been encouraging. An expanded cohort of the combination chemotherapy is underway. No significant financial relationships to disclose.
Hepatocellular carcinoma presenting with lung metastasis: Clinical characteristics and prognostic factors
Authors: Kojima Y. , Ueno H. , Okusaka T. , Morizane C. , Kondo S. , Hagihara A. , Iwasa S. 
Published: August 2020

e15604 Background: The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) has been limited, but sorafenib has changed the strategy treating for metastatic HCC. The lung is one of the most common metastatic sites for HCC. Therefore, we focused on clinical features and prognostic factors of HCC patients (pts) with lung metastasis in this study. Methods: Between January 2000 and April 2008, 1,117 HCC pts were admitted into our division. During this period, extrahepatic metastasis was detected in 286 pts, and the initial metastatic site was lung in 130 pts. The relationships between the characteristics of these pts at the time of lung metastasis detection and prognosis were examined. Results: There were 107 males and 23 females. Median age was 64 years. The Child-Pugh classification was A in 84 pts, B in 32 pts. HCV Ab was positive in 57 pts, HBs Ag was positive in 46 pts, and both were negative in 27 pts. The median survival time of all pts was 298 days. Univariate analysis revealed 12 of the 20 variables evaluated to be significantly associated with survival time: number of lung metastasis, presence of intrahepatic HCC, maximum size of intrahepatic HCC, presence of tumor thrombus, AFP, PIVKA II, albumin, prothrombin time, ALP, presence of ascites, Child-Pugh classification, and previous history of hepatic resection. Multivariate analysis using the Cox proportional hazards model demonstrated a lower number (≤5) of lung metastases (p<0.0001), the absence of intrahepatic HCC (p=0.0002), and the absence of ascites (p=0.0339) to be independent favorable prognostic factors. Conclusions: These results may provide useful reference data for determining treatment strategies and planning further clinical trials involving HCC patients with lung metastasis. No significant financial relationships to disclose.
Locoregional therapies as a bridge to transplant in patients with hepatocellular carcinoma
Authors: Sakaria S. S. , Dhanasekaran R. , Pankonin M. , Parekh S. , Kauh J. S. , Kim H. S. 
Published: August 2020

e15608 Background: Orthotopic liver transplantation (OLT) has been widely established as the definitive treatment for patients with HCC who fit within the Milan criteria. The limited availability of donor organs results in prolonged waiting periods leading to tumor progression and potential disqualification for OLT. As a result, there has been a rising interest in locoregional therapies that may stall tumor progression until a donor organ is available for transplantation. Methods: We reviewed patients with a diagnosis of HCC on the transplant list between 1998 and 2008. Of these patients, 72 patients received locoregional therapies (LRT). The various LRT consisted of transcatheter therapy alone (29 patients); combination transcatheter therapy and radiofrequency ablation (RFA) (33 patients), and RFA alone (10 patients). Kaplan Meier method with the log rank test and Cox proportional hazards method were used for survival analysis. Results: Of the 72 patients, 71% (51/72) were transplanted and 29% (21/72) dropped out. The reasons for drop-out from the transplant list included tumor progression (4.2%); condition deteriorated (11.1%); death (6.9%); refusal of transplant (2.7%); other causes (4.2%). The long term survival rates in the transplanted patients at 1 yr, 2 yrs and 5 yrs is 90%, 87% and 72%. The long term survival in the non-transplanted patients at 1 yr and 2 yrs is 47% and 33% respectively. Mean duration from the first LRT to OLT was 126 days (SD 208). In patients who dropped out, mean duration from the first LRT to the removal date was 143 days (SD 256). The mean post transplant follow-up period was 758 days (SD 527). No recurrence was found in the post transplant follow- up. Conclusions: Locoregional therapies can be effectively used as a bridging therapy to treat patients with HCC awaiting transplant. The long term recurrence-free survival in patients who received OLT after bridging therapies demonstrated 5-year survival rates of 72% and no recurrence after transplant. No significant financial relationships to disclose.
Prognostic factors of survival in 236 advanced hepatocellular carcinoma patients enrolled in prospective clinical trials of systemic therapy
Authors: Lin Z. , Chang D. , Shao Y. , Hsu C. , Hsu C. , Yeh K. , Yang C. , Hong R. , Cheng A. 
Published: August 2020

e15632 Background: Hepatocellular carcinoma (HCC) is a common malignant disease. Promising results of prospective clinical trials using systemic therapy for patients with advanced HCC are emerging. The aim of this study was to explore prognostic factors of survival in advanced HCC patients eligible for clinical trials of systemic therapy. Methods: From December 1990 to July 2005, 236 patients with unresectable HCC were enrolled into 6 phase II trials of systemic therapy using the following regimens: (1) oral etoposide + tamoxifen, (2)doxorubicin + tamoxifen, (3)IFN-α2b + doxorubicin + tamoxifen, (4)pegylated liposomal doxorubicin, (5)thalidomide, and (6)arsenic trioxide. Univariate and multivariate analyses of 23 relevant clinical characteristics/staging systems were used to identify prognostic factors of survival. Results: Baseline characteristics: median age 55; male/female: 192/44; HBsAg(+) 71%; anti-HCV(+) 30%; Okuda stage I/II/III: 42%/55%/3%; AJCC stage III/IV: 30%/61%; BCLC stage B/C/D: 1%/94%/5%; CLIP score 0–3/4–6: 70%/30%; portal vein thrombosis 53%; extrahepatic metastasis 59%; prior chemoembolization 46%. The objective response rate according to WHO criteria was 11.4%. The median overall survival was 118 days (95% CI, 103–133). In the multivariate analysis, significant predictors of a shorter overall survival were: HBsAg(+) with a hazard ratio (HR) = 1.808 (95% CI, 1.121–2.916; P= 0.015), symptomatic with HR = 1.745 (95% CI, 1.072–2.840; P= 0.025), ECOG≥2 with HR = 1.763 (95% CI, 1.040–2.988; P= 0.035), and high BCLC stage with HR = 3.282 (95% CI, 1.129–9.541; P= 0.029). Conclusions: Patients with advanced HCC who are eligible for systemic therapeutic trials have patient- and disease-related prognostic factors. Positive HBsAg, symptomatic, ECOG performance≥2, and high BCLC stage predict a shorter overall survival. No significant financial relationships to disclose.
Multimodality salvage therapy for anal cancer failing standard chemoradiation
Authors: You Y. N. , Larson D. W. , Dozois E. J. , Nelson H. , Antpack Filho E. , Klein K. , Miller R. C. 
Published: August 2020

e15635 Background: Most squamous cell carcinomas of the anal canal (SCC) respond to chemoradiation, but effective therapy for locally-invasive(T4) or recurrent disease that fails standard chemoradiation and/or salvage abdominoperineal resection (APR) has not been clearly delineated. A multimodality approach including chemoradiation, extended pelvic resection and intraoperative radiation therapy (IORT) was assessed for survival impact and treatment morbidity.morbidities. Methods: A prospective registry including 26 patients with locally-invasive or recurrent disease treated between 1993 and 2007 was reviewed. Primary endpoint was overall survival (OS), obtained from prospectively collected patient questionnaires and medical record review, and analyzed by the Kaplan-Meier method. Short (60-day postoperative) and long-term (median followup: 1.6 years; 5.3 years among survivors) complications were assessed. Results: Patients (median age: 51 years) presented with (1) locally-invasive disease that persisted despite initial standard chemoradiation (n=10, 39%), (2) disease that recurred after initial standard chemoradiation (n=10, 39%; median 1.7 years to recurrence), or (3) re-recurrence after a salvage APR (n=6, 23%; median 1.3 years since APR). All patients received chemotherapy and external beam radiation preoperatively, and 19% received additional postoperative chemoradiation. Gross pelvic disease was completely resected in all (R0 in 73%; R1 in 27%). IORT (750–3250cGy) was delivered at single (92%) or two sites (8%). Median overall survival (OS) was 1.7 years. Five-year OS were: 50%, 10%, and 22% for patients with locally-invasive, recurrent, and re-recurrent disease respectively. Short-term complications predominantly related to the perineal wound. Fifteen patients reported long-term complications (>grade3): bowel obstruction in 8 (1 requiring operation), perineal wound fistula/non-healing in 9, leg paresthesia in 5, hydronephrosis in 3. Conclusions: For select patients with locally-persistent or recurrent SCC who fail standard primary treatment, a multimodality approach involving chemoradiation, extended pelvic resection and IORT offers a chance for improved survival. No significant financial relationships to disclose.
Prognostic impact of the NFKB1 insertion/deletion promoter polymorphism on survival in patients with surgically resected gastric cancer
Authors: Kim S. , Kim J. , Chae Y. , Sohn S. , Moon J. , Kang B. , Chung H. , Yu W. , Baek J. 
Published: August 2020

e15638 Background: The present study analyzed the functional insertion/deletion polymorphism in the promoter region of NKFB1 gene and their impact on the prognosis for patients with gastric adenocarcinoma. Methods: Five hundred and three consecutive patients with surgically resected gastric adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and the -94 insertion/deletion ATTG polymorphism of NFKB1 determined using a PCR- RFLP assay. Results: The NFKB1 promoter gene polymorphism was successfully amplified in 97.8% of the cases. There were no sexual differences in relation to the genotype and allele. No correlation was observed between the frequency of the genotype or allele and the T, N, or M stage. The multivariate survival analysis showed no association between the NFKB1 -94 insertion/deletion promoter polymorphism and the disease-free survival or overall survival of the patients with gastric cancer. Conclusions: The functional NFKB1 promoter polymorphism was not found to be a prognostic marker for Korean patients with surgically resected gastric adenocarcinoma. No significant financial relationships to disclose.
Case study of a flexible bayesian design in a phase II study in patients with resected pancreas cancer
Authors: Harrell F. E. , Rodell T. , Apelian D. 
Published: August 2020

e15651 Background: This presentation will describe a Bayesian flexible design for an ongoing randomized, placebo controlled phase II trial in newly diagnosed, resected pancreas cancer comparing gemcitabine plus therapeutic vaccine (GI-4000) vs. gemcitabine alone. The design allows for infinitely many looks at the data, possible study expansion, and conversion to adaptive allocation. Unlike frequentist approaches, the Bayesian procedure does not require penalizing the final analysis for earlier analyses nor does it require down-weighting of data collected before the decision to expand the study. The same analysis procedure is used for final and interim analyses, whereas there is no consensus in the frequentist approach for how to analyze an expanded study. Methods: Our primary analysis is based on a Bayesian Cox proportional hazards model using a skeptical prior distribution. The endpoint is time to recurrence or death. Evidence for efficacy is taken to be a posterior probability of efficacy ≥ 0.95 at any analysis time, where ‘efficacy’ means a true hazard ratio < 1.0. The planned rule for expanding the study is a probability of efficacy ≥ 0.7 prior to the last pre-planned analysis. Results: This ongoing study remains blinded. Results will include statistical methods (including simulations to assess study properties of the design) and experience in collaborating on the design with the FDA. Conclusions: In the frequentist approach, computing the probability of getting a result as or more impressive than that observed if there is truly no treatment effect (the P-value) requires contemplating experiments that were never carried out and analyses that were never done. The Bayesian approach offers the advantage of computing only ‘forward’ probabilities (Bayesian posterior probabilities) and conditioning only on what has been observed up to the time of analysis. There is no requirement to assume unknowable information such as the true population treatment effect. The adaptability afforded by Bayesian trial design can greatly enhance the likelihood of gaining useful clinical data from phase II trials. [Table: see text]
Prognostic relevance of ribonucleotide reductase small subunit p53R2 in pancreatic cancer
Authors: Chung V. M. , Liu X. , Chu P. , Yen Y. 
Published: August 2020

e15655 Background: Pancreatic cancer has the worst survival of any solid tumor, with most patients presenting with metastatic disease. Even after surgical resection the median survival is only 20 months suggesting micrometastatic disease. Ribonucleotide reductase is a critical enzyme in DNA synthesis and repair. Previous studies have shown that ribonucleotide reductase M2 (RRM2) subunit is associated with invasion and metastasis. Even though p53R2 has 80% homology to RRM2, its role is quite different. Here we report on the prognostic relevance of p53R2 in pancreatic cancer. Methods: Archived pathology specimens were obtained from 30 patients and immunohistochemistry for p53R2 performed on an IRB approved protocol (#06253). Clinical data was obtained by chart review and log-rank and Cox hazard proportional models were used to analyze overall and disease-free survival. Cell culture analysis was performed to further evaluate the role of p53R2. Utilizing a Matrigel chamber, invasive MiaPaCa-2 cells were collected for comparison to parental cells. Results: The median overall survival (OS) was 13.2 months (p53R2+) vs 8.5 months (p53R2-) (p=0.01). Disease free survival (DFS) was 12.4 vs 8.5 months respectively (p<0.05). By Western analysis, invasive cells have a higher protein level of RRM2 compared to parental cells. Interestingly, the protein level of p53R2 was low in the invasive cells suggesting an opposing role. To confirm this we inhibited p53R2 using siRNA which enhanced the migration ability of Mia PaCa-2 cells. Conclusions: Patients with p53R2 expression have improved disease-free and overall survival suggesting this may be used as a prognostic marker in pancreatic cancer patients. No significant financial relationships to disclose.
Systematic meta-analysis on percutaneous ethanol injection and percutaneous acid injection for the treatment of early HCC: A Cochrane analysis
Authors: Schoppmeyer K. , Weis S. , Mossner J. , Fleig W. E. 
Published: August 2020

e15657 Background: Hepatocellular carcinoma (HCC) is the fifth most common global cancer with high geographical variability. When HCC is detected early, percutaneous approaches such as percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), and radiofrequency thermal ablation (RFTA) have curative potential and represent low invasive alternatives to surgery. The role of percutaneous ethanol or acetic acid injection and other percutaneous interventions except RFTA has not been addressed in a systematic metaanalysis. The objective was to evaluate the effects of PEI and PAI for early HCC. Methods: A systematic search was performed in EMBASE, Cochrane Central, The Cochrane Hepato-Biliary Group Controlled Trials Register, Medline and Scopus as well as a handsearch of meeting abstracts. Only randomised controlled trials were included. RFTA studies were not considered. Primary endpoint was overall survival, secondary endpoints were cancer free survival, number and type of adverse events, duration of hospital stay, and quality of life. Results: 3 studies covering 261 patients were identified. Two studies compared PEI with PAI. 91 and 94 patients with one to three HCC-nodules ≤ 3cm underwent PEI and PAI, respectively. Overall survival (HR 1.47; 95% CI 0.68 to 3.19) and cancer free survival (HR 1.42; 95% CI 0.68 to 2.94) were not significantly different after treatment by PEI versus PAI. Both treatments were safe with no serious adverse events reported and modest pain being the most frequent adverse event. Data on the duration of hospital stay were inconclusive and data on quality of life not available. One study compared PEI with surgery. 38 patients were allocated to each treatment arm. There was no significant difference in survival (HR 1.57; 95% CI 0.53 to 4.61) and cancer free survival (HR 1.35; 95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group but 3 postoperative deaths occurred in the surgery arm. Conclusions: PEI and PAI are similarly effective and safe in patients with one to three small (≤ 3 cm) HCC nodules. Although the evidence is weaker, the beneficial effect of PEI is comparable to that of segmental liver resection and thus should be used preferentially due to its low morbidity and mortality. No significant financial relationships to disclose.