bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors (PF) in advanced hepatocellular carcinoma (AHCC): Multivariate analysis and comparison between staging systems (SS) in patients (pts) treated at Memorial Sloan-Kettering Cancer Center (MSKCC)
Authors: Huitzil F. D. , Capanu M. , Jacobs G. , Smith W. , O’Reilly E. , Shah M. , Schwartz G. K. , Saltz L. B. , Kelsen D. P. , Abou-Alfa G. K. 
Published: March 2020

4601 Background: Several SS have been proposed in hepatocellular carcinoma. These include TNM, Okuda, Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), and Barcelona Clinic Liver Cancer (BCLC). There is no consensus as to what constitutes the best SS for use by oncologists for pts with AHCC with no locoregional therapy options. We propose to define the PF and compare SS in this patient population. SS may help select pts for systemic therapy, predict outcome, and help in clinical trial design for AHCC. Methods: We retrospectively identified pts with AHCC treated at MSKCC between 2001 and 2006. Clinical, laboratory, tumor characteristics and all four SS were recorded. Survival (S) was measured from the date of development of AHCC to the date of death. S was estimated using Kaplan-Meier’s method, differences in S were tested using the log rank test. A Cox regression model was used for the multivariate analysis. A second Cox regression was done to compare SS and was expressed using the Akaike information (AI) criterion. AI helps determine which SS is the most informative of S. A low AI is favorable. Results: We identified 280 pts. Data on the first 101 pts analyzed are presented. Median age 61 years; 71% males, 29% females; 60% Caucasians, 9% Black, 24% Asians and 5% Hispanics. Etiologies included HCV 24%, HBV 38%, and alcohol 22%. Child Pugh score: A in 65% and B in 29% of pts. Multivariate analysis independent PF for S were albumin (p=0.0358), alkaline phosphatase (ALP) (p=0.001), identified etiology (p=0.008), abdominal pain (p=0.001) and liver tumor extent (more or less than 50% of the liver) (p=0.0043). AI ranked SS as follows: TNM 6th (588.991), TNM 5th (591.373), BCLC (541.095), Okuda (540.490), CLIP (537.8), and CUPI (526.483). CUPI S was 19.47 months (m) for low, 5.89 m for medium, and 1.36 m for high risk pts. Conclusions: Pts with AHCC who are treated by oncologists in this US-based population have distinct PF. CUPI provided the best prognostic information for our patient population. CUPI may be suggested as the SS to use clinically for AHCC. These results need prospective validation. No significant financial relationships to disclose.
Preliminary results of a phase I/II study in pancreatic carcinoma, malignant melanoma, and colorectal carcinoma with the TGF- β2 inhibitor AP 12009
Authors: Oettle H. , Seufferlein T. , Schmid R. , Luger T. , Ludwig S. , Schmaus S. , Wuerth G. , Heinrichs H. , Schlingensiepen K. 
Published: March 2020

4607 Background: TGF-β2 plays a pivotal role in tumor progression as it regulates key mechanisms, namely immunosuppression, metastasis, angiogenesis, and proliferation. The TGF-β2 inhibitor AP 12009 has shown clinical efficacy including complete and long-lasting remissions in patients with high-grade glioma. Methods: The currently ongoing clinical phase I/II study AP 12009-P001 is an open-label, multicenter, dose-escalation study. AP 12009 is being administered intravenously in adult patients with pancreatic carcinoma (PC, stage IVA/IVB), metastatic melanoma (MM, stage III/IV), or advanced colorectal carcinoma (CRC, stage III/IV). Primary endpoint is determination of the maximum tolerated dose (MTD). 3 to 6 patients per cohort (dose group) were enrolled into this dose escalation study. Results: So far, 17 patients have been treated in four dose groups, 11 patients with PC, 2 with MM, and 4 with CRC. Per cycle, AP 12009 was applied as a continuous i.v. infusion at weekly intervals in an out-patient setting. The 17 patients received one to ten cycles of AP 12009 (mean: 2.8). At the current stage, no (possibly) drug related serious adverse event (SAE), and only 17 (possibly) drug related adverse events (AEs) in eight patients have been observed. The 17 patients received one to ten cycles of AP 12009. Three dose-limiting toxicities (DLTs) occurred in the 4th dose group (exanthema grade 3 in one patient, thrombocytopenia grade 3 in two patients) and consequently, the MTD was determined as being 160 mg/m2/day with the current administration schedule. One patient suffering from MM stage IV is still alive 64 weeks after start of treatment. Moreover, one PC patient (stage IV) from the 2nd cohort is still after 72 weeks, having experienced a complete response. Further dose escalation studies in PC, MM, and CRC patients using a modified schedule are currently in preparation. Conclusions: In conclusion, encouraging case reports from the phase I/II study along with a good safety profile form a rational basis for the use of the TGF-β2 inhibitor AP 12009 as targeted therapy for advanced solid tumors such as PC, MM and CRC. No significant financial relationships to disclose.
Phase I/II trial of docetaxel plus oxaliplatin and 5-fluorouracil (D-FOX) in patients with untreated, advanced gastric or gastroesophageal cancer
Authors: Ajani J. A. , Phan A. , Ho L. , Tetzlaff E. D. , Baker J. , Wei Q. 
Published: March 2020

4612 Background: Docetaxel combined with cisplatin/5-fluouracil resulted in significantly longer time-to-progression and survival but also 30% rate of complicated neutropenia (JCO 2006; 24:4991). To improve the safety profile of docetaxel-based therapy, we studied docetaxel with oxaliplatin/5-fluorouracil (D-FOX) to establish the first-cycle MTD (phase II trial to follow). Methods: Patients with histologic proof of gastric or gastroesophageal adenocarcinoma with untreated stage IV cancer were eligible. ECOG PS of <2, near-normal organ function, and written consent were other eligibility criteria. The initial doses of oxaliplatin (85mg/m2) and 5-fluorouracil (2.2g/m2 as 48-hour infusion), given every 2 weeks, were kept constant. Docetaxel was started at 20mg/m2 (Level 1) every 2 weeks in a typical 3x3 phase I design. Subsequent levels (+5mg/m2 every 4 weeks) were added. Fatigue, incompletely treated nausea, and oxaliplatin/5-flurouracil-related toxicities were excluded to determine the MTD. Results: A total of 36 patients have been treated. Currently, docetaxel dose is 47.5mg/m2 every 2 weeks (Level 11). MTD was not reached at Level 10. Overall, grade 3 or 4 first-cycle toxicities have occurred in <5% of patients and without complicated neutropenia. Fifteen of 34 patients have had a confirmed partial response, 13 had stability, and 6 patients had progression. Conclusions: The MTD of D-FOX has not yet been established but its safety profile (D-FOX with 45mg/m2 of docetaxel every 2 weeks) is excellent and the regimen is quite active against untreated gastric or gastoresophageal cancer. Translation studies and additional clinical data will be presented. Supported in part by sanofi-aventis pharma. [Table: see text]
Association between high tumor CCL2 expression and poor survival in patients with resectable pancreatic cancer
Authors: Yan L. , Hu Y. , D’Andrea M. R. , Towers M. A. , Wang Y. , Kesavan P. , DeWitte M. , Nakada M. T. , Ahrendt S. 
Published: March 2020

4618 Background: CCL2 (MCP-1) is a chemoattractant protein highly expressed in a variety of cancer types. The expression level of CCL2 has been linked to aggressive disease progression, early dissemination, and poor survival in certain cancers. Therefore, we assessed the potential association between CCL2 expression and patient prognosis in pancreatic cancer. Methods: Cylindrical tissue cores from a large retrospective, nonrandomized series covering 133 patients with resected pancreatic cancer were used to build a tissue microarray. CCL2 expression was determined using immunohistochemistry. Results: High intratumoral CCL2 expression and low intratumoral CCL2 expression were present in 44 (33%) and 89 (67%) tumors, respectively. Kaplan-Meier median survival among patients with low intratumoral CCL2 expression (19.1 months) was longer than that among those with high CCL2 expression (12.1 months). In multivariate analysis, more advanced pathological stage [risk ratio (RR) = 1.57; P = 0.038], poorly differentiated histology (RR = 1.68; P = 0.019), and high CCL2 expression [RR = 1.62; 95% confidence interval (CI) = 1.05–2.49; P = 0.028] were independent predictors of mortality. Conclusions: High CCL2 expression is a marker of poor prognosis in resected pancreatic cancer. [Table: see text]
Initial findings from the Memorial Sloan-Kettering Early Onset and Familial Gastric Cancer Registry (EOFGCR)
Authors: Harlan M. , Sheehy E. , Randazzo J. , Schrag D. , Kemeny M. M. , Kelsen D. P. , Shah M. A. 
Published: March 2020

4619 Background: Hereditary Diffuse Gastric Cancer(HDGC) is an autosomal dominant cancer susceptibility syndrome defined as having 2 or more diffuse GC(one of which diagnosed before the age of 50) or 3 or more diffuse GC in 1st or 2nd degree relatives. A germline mutation in E-Cadherin(CDH1) is found in 20–30% of HDGC families. HDGC is responsible for 30% of all hereditable GC. The genetic cause for the remaining 70% of hereditable GC is unknown. We created a registry for early onset and familial gastric cancer to capture epidemiologic and family history data matched with DNA and tissue to characterize various phenotypic and risk factor profiles and their associations with HDGC and other non-HDGC hereditable GC. Methods: Patients with a family history(patients with one first degree relative or 2 second degree relatives with GC) or who developed GC at an early age(age < 50) were eligible for registry participation. Participants complete a GC risk factor questionnaire, family history, provide blood and tissue for repository, and meet with a genetics counselor to consider germline CDH1 mutation testing. Results: 57 patients have enrolled since January 2006: 36 patients with early onset, 21 with familial GC. Eleven patients have a family history meeting HDGC criteria, two with known CDH1 mutations. Three of the 11 HDGC families are from Ecuador. GC risk factor questionnaires are available from 46 patients(81%), see table . Although no novel CDH1 mutations were found in 13 fully sequenced patients, 4 patients(31%) were found to have uncommon genotypes, including two with early onset of disease diagnosis (ages 22 and 34) with multiple variants in CDH1. Conclusions: HDGC patients tend to have more high risk features including smoking history, use of salt, and H. pylori infection. We have identified a cluster of patients with HDGC of Ecuadorian descent. Genetic variation in CDH1 suggests that novel haplotypes may be associated early onset GC risk.(Supported by the DeGregorio Family Foundation) [Table: see text] No significant financial relationships to disclose.
Clinical and molecular determinants of survival in pancreatic cancer patients treated with second line chemotherapy: results of an Italian/Swiss multicenter survey
Authors: Mancuso A. , Sacchetta S. , Saletti P. , Tronconi C. , Milesi L. , Garassino M. , Martelli O. , Labianca R. , Cavalli F. , Sternberg C. N. 
Published: March 2020

4622 Background: The impact on survival of palliative second-line therapy in pancreatic cancer has not been clarified and clinical/molecular predictive factors are needed in order to decide which therapeutic regimens may be effective. Methods: Clinical records of 160 Gemcitabine resistant/refractory pancreatic cancer patients (pts) treated in 11 medical oncology departments in Italy and Switzerland were reviewed. All pts received a second line regimen from June 1997 to February 2006. There were 99 males, 61 females, median age 62 years (range 34–78) and median ECOG performance status (PS): 1 (range 0–2). 16 different salvage regimens were administered consisting of monotherapy with fluoropyrimidines in 59% of cases and combinations of platinum- salts/fluoropyrimidines in 36%. Fluoropyrimidines combinations with bevacizumab, irinotecan and mitomycin C were administered in the remaining 5%. ERCC-1 expression was examined by performing immunohistochemical staining in pts treated with platinum-salts. Results: Second line chemotherapy produced partial responses (PR) in 16 (10%) and stable disease (SD) in 40 pts (25%) by RECIST criteria. The median progression free survival (PFS) was 2.65 months. Multivariate analysis revealed that the most important prognostic factor for PFS was PS at the beginning of second line therapy (Second line PFS PS=0–1 vs PS=2: 78 days vs 48 days, p<0.05, log-rank test). Pts who had responded (PR) to first-line Gemcitabine were more likely to respond or attain stable disease after second-line treatment, with a PFS of 2.6 vs 1.6 months (p<0.05, log-rank test). The overall survival (OS) for all evaluable pts was 11.5 months and 1-year survival was 45%. Among 57 pts treated with platinum-containing doublets, a low ERCC1 level (28/57 pts) was highly predictive of longer survival (11.9 versus 9.9 months, p<0.05 log-rank test). Conclusions: These results suggest that fluoropyrimidine-based salvage regimens have marginal activity and should be considered only in pts with a good PS who have responded to first line chemotherapy. ERCC-1 expression should be further evaluated as a predictive test to select patients who may benefit from platinum/fluoropyrimidine salvage regimens. No significant financial relationships to disclose.
Comparison of squamous cell carcinoma of the canal anal (SCCA) prognosis in patients infected or not by human immunodeficiency virus (HIV)
Authors: Mathieu N. , Aparicio T. , Roudot-Thoraval F. , Lemarchand N. , Bauer P. , Hennequin C. , Mitry E. , Romelaer C. , Abramowitz L. , Sobhani I. 
Published: March 2020

4632 Background: Incidence of SCCA is increasing promoted by HIV infection. Previous small series of SCCA revealed a worst prognosis in HIV+ than in HIV- patients. Few data are available since the use of highly active antiretroviral therapy (HAART) in HIV patients. The aim of the study was to compare clinical outcome of patients recently treated for SCCA according to HIV status. Methods: Retrospective study in 6 hospitals. all consecutive patients treated for SCCA from January 1998 to October 2004 were included. Clinical outcome and pattern of care according to HIV status were compared. Results: 151 patients were included, 44 (29%) of them were HIV infected. Median follow-up was 27 (16–44) months. HIV+ patients were youngest (45 vs 62 years old, p<0.001) and only male (100% vs 27%, p<0.001). There were no significant difference in tumor stage I : 37.5 vs 25%, II : 48 vs 42.5%, IIIa : 7.5 vs 16.5%, IIIb : 12.5 vs 5% and IV : 0 vs 6% according to HIV+ or HIV- respectively. The treatments performed in HIV+ and HIV- patients were: Pelvic radiotherapy in 86 vs 91% (ns) delivering a median dose of 48 and 46 Gray. A boost in reduced fields or brachytherapy was performed in 58% vs 64% (ns). Concomitant chemotherapy (5-fluorouracile and cisplatin) was administered in 52% vs 56% (ns). Dose intensity of 5-fluorouracile and cisplatin was similar in both group. Grade 3–4 toxicity of chemoradiotherapy was observed in 11% vs 10% (ns). Complete response was obtained in 82 vs 75% (ns) and surgery (colostomy or abdominoperineal resection) was performed in 2.4% vs 7.6% of the patients (ns). During the follow-up local or metastatic recurrence occurred in 32% vs 22% of the patients (ns). The 3 years disease free survival were 77% vs 67% (ns) and 3 years overall survival were 85% and 84% (ns). Among HIV+ patients, 42/44 were on HAART, the survival was not modified by the duration of infection, viral load and CD4 count. Conclusions: The clinical outcome of HIV+ patients with SCCA is now similar to HIV- patients. The same therapeutic guidelines should be applied in both population. This improvement of prognosis is probably due to extensive use of HAART in HIV+ patients. No significant financial relationships to disclose.
Circulating tumor cells detected in patients with gastrointestinal cancers associate with tumor stage and response to chemotherapy
Authors: Hiraiwa K. , Takeuchi H. , Kitagawa Y. , Hasegawa H. , Saikawa Y. , Ando T. , Irino T. , Yoshikawa T. , Ishii S. , Kitajima M. 
Published: March 2020

4635 Background: Circulating tumor cells (CTCs) in metastatic breast cancer has been reported to correlate with shorter overall survival. The purpose of this study was to clarify the clinical significance of CTCs in gastrointestinal cancers. Methods: CTCs of 108 patients with stage III or IV gastrointestinal cancers and 38 healthy volunteers were measured by use of the CellSearch system. Correlation between CTC counts and clinicopathologic variables was examined. Results: The number of CTCs in stage IV patients (23.0 ± 109.1) was significantly larger than that in healthy donors (0.1 ± 0.2) and that in stage III patients (0.4 ± 1.8) (p < 0.001). =2 CTCs were more frequently found in stage IV patients (41.6%) than in healthy donors (0%) and in stage III patients (3.2%) (p < 0.001). =2 CTCs in gastric or colorectal cancer had significant correlation with peritoneal dissemination (p = 0.029). =2 CTCs in esophageal cancer had significant correlation with pleural dissemination (p = 0.030). In 10 of 32 CTC positive (=2) patients with stage IV gastrointestinal cancers, CTC was measured before initiation of a new line of chemotherapy and more than 3 weeks after initiation of therapy. The change in CTCs correlated with disease progression and reflected chemotherapeutic effect. Conclusions: This study suggested measurement of CTCs in gastrointestinal cancer patients shows promise as a tool for judging advanced tumor stage, predicting peritoneal or pleural dissemination and monitoring response to chemotherapy. No significant financial relationships to disclose.
Transarterial infusion chemotherapy alone versus transarterial chemoembolization for the treatment of hepatocellular carcinoma: Results of a multicenter randomized phase III trial
Authors: Okusaka T. , Sato T. , Hinotsu S. , Shioyama Y. , Kasugai H. , Tanaka K. , Kudo M. , Saisho T. , Osaki Y. , Sata M. , Fujiyama S. 
Published: March 2020

4643 Background: Transarterial chemoembolization (TAE) is widely used for patients (pts) with hepatocellular carcinoma (HCC) although evidence of a survival benefit remains controversial. A multicenter phase III trial was designed to compare the effects of TAE and transarterial infusion chemotherapy alone (TAI) on overall survival. Methods: Pts with newly diagnosed unresectable HCC were randomly assigned to either the TAE or the TAI group, stratified according to center and the serum alpha-fetoprotein level. Zinostatin stimalamer (SMANCS), up to a maximum of 6 mg, plus lipiodol emulsion with or without gelatin sponge was injected into the hepatic artery. Treatment was repeated when a follow-up computed tomography examination showed the appearance of new lesions in the liver or the regrowth of the treated tumors. Based on our previous phase II studies, reporting a 2-year survival rate of 80% in pts treated with TAE and of 60% in pts treated with TAI, 80 pts were needed in each group to achieve a level of statistical significance of 5% (2-sided) and a power of 80%. Results: From October 1999 to June 2003, 79 pts were assigned to the TAE group and 82 pts to the TAI group. The two groups were well balanced with regard to their baseline characteristics. The total number of treatment courses was 170 with a mean of 2.2 courses per patient (range, 1–9 courses) in the TAE group and 193 with a mean of 2.4 courses (range, 1–6 courses) in the TAI group. As of June 2005, 51 pts in the TAE group and 58 pts in the TAI group had died. The median overall survival time was 646 days in the TAE group and 679 days in the TAI group. No significant difference in survival was seen between the two groups (p=0.383). The mortality rate reduction for overall survival was 15.8% (95% CI, -24.1% to 42.9%) for the TAE relative to the TAI alone. Conclusions: This study suggests that treatment intensification as a result of embolization did not increase survival, compared with SMANCS transarterial chemotherapy alone, in pts with HCC. No significant financial relationships to disclose.
Imaging and therapy for Epstein-Barr virus-associated gastric cancer
Authors: Fu D. , Chong J. , Foss C. , Fox J. , Wang S. , Green G. , Chen J. , Lemas M. V. , Pomper M. , Ambinder R. 
Published: March 2020

4644 Background: Epstein-Barr virus (EBV) has been identified in a wide variety of malignancies, including gastric carcinomas. The virus encodes kinases that phosphorylate nucleoside analogs such as 2’-deoxy-2’-fluoro-5-iodo-1-beta-D- arabinofuranosyluracil (FIAU). We hypothesized that it might be possible to use the viral enzyme to specifically concentrate [125I]FIAU or [131I] FIAU in tumor cells harboring virus and thus deliver imaging and therapeutic radiation. Bortezomib is a potent stimulator of viral kinase expression in EBV tumor cell lines. Methods: We imaged lytic induction in vivo and evaluated the effect of [131I] FIAU on human cancer xenografts in SCID mice. These include a tumor line engineered to constitutively express the EBV thymide kinase (EBVTK), and a control engineered with a sham vector (SHAM), as well one EBV-associated human gastric tumor (KT tumor). Mice were treated with buffer, bortezomib (2μg/g), or radiolabeled FIAU or radiolabeled FIAU and bortezomib in combination. For imaging, mice, [125I]-FIAU and SPECT/CT were used. For therapy, 131I-FIAU was used and tumor dimensions were monitored with calipers. Results: SPECT/CT imaging with [125I]-FIAU of tumor-bearing SCID mice showed selective concentration of radiotracer in tumor tissue in EBVTK (3/3) and in EBV-associated KT tumors (3/3) when animals were pretreated with bortezomib. Treatment with buffer had no effect on 3 EBVTK tumors and 3 SHAM tumors all of which increased in volume. Treatment with 1.6 mCi of [131I]-FIAU alone led to tumor response in 3/3 mice with EBVTK tumors and 0/3 mice with SHAM tumors. Treatment with [131I]-FIAU alone had no effect on EBV KT tumor xenografts (0/3) and all tumors increased in volume. Treatment with bortezomib induced modest responses in all KT tumors. However, treatment with bortezomib and [131I]-FIAU led to marked tumor regression (>80%) in EBV-associated KT tumors (3/3). Conclusions: Treatment with bortezomib leads to selective concentration of radiolabeled FIAU in the EBV-associated tumor xenografts. In combination with [131I]-FIAU it leads to tumor regression. No significant financial relationships to disclose.