bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant chemoradiation therapy for pancreatic adenocarcinoma: Impact of family history on outcome
Authors: Herman J. M. , Pawlik T. J. , Swartz M. , Yu H. M. , Schulick R. , Winter J. , Laheru D. , Hruban R. , Klein A. P. 
Published: March 2020

15044 Background: The objective of the current study was to examine the impact of a family history of pancreatic adenocarcinoma (PCA) on the outcome of patients receiving adjuvant chemoradiation therapy (CRT) following pancreaticoduodenectomy (PD). Patients and Methods: Between August 1993 and February 2005, 902 patients underwent PD for pancreatic adenocarcinoma. Following PD, 405 patients received no adjuvant CRT, while 346 patients received CRT. Another 151 patients were excluded because they received protocol treatment, neoadjuvant CRT, or were lost to follow-up. Patients who received adjuvant CRT were treated with 5-FU (97.4%) based CRT (median dose 50 Gy) and maintenance 5-FU or gemcitabine. Survival was estimated using the Kaplan-Meier method and differences in survival were examined using the log-rank test. Cox regression analysis was used to control for family history. Results: Of the 751 patients included in the study, 158 (21%) patients had a known family history of pancreatic adenocarcinoma (only one family member n=119; >=2 either first or second degree relatives, n=39). Clinicopathologic characteristics of patients with a family history of PCA were similar to those of patients who did not have a family history (age, race, positive lymph node status, primary tumor size, and proportion receiving adjuvant CRT; all P>0.05). In an analysis of the entire patient cohort, adjuvant CRT was associated with an improvement in median overall survival compared with no adjuvant CRT (21.0 months vs. 14.6 months, respectively; P= 0.001). Family history of PCA (>=1 family member) was not associated with overall survival (positive family history, 20.0 months vs. negative family history, 17.3 months; P = 0.12). Family history of PCA also did not modify the effect of CRT on overall survival. Specifically, on multivariate analysis, after stratifying on family history (>=1 family member), CRT remained significantly associated with an improved survival (Hazard ratio=0.71; P=0.001). Conclusion: Adjuvant 5-FU based CRT improves the median survival of patients with resected pancreatic adenocarcinoma. The improvement in median survival associated with adjuvant CRT was independent of a familial history of pancreatic adenocarcinoma. No significant financial relationships to disclose.
Portal vein and systemic thromboses in hepatocellular carcinoma
Authors: Connolly G. C. , Khorana A. , Mantry P. , Bozorgzadeh A. , Abt P. , Chen R. , Hyrien O. 
Published: March 2020

15048 Background: Hemostatic activation may be important for tumor growth and metastasis. Hepatocellular carcinoma (HCC) is commonly associated with portal vein thrombosis (PVT). Very little is known about factors predictive for PVT in patients with HCC or its correlation with systemic venous thromboembolism (VTE). Methods: We conducted a retrospective chart review of 194 patients diagnosed with HCC at the University of Rochester between 1998 and 2004. The primary endpoints of this study were presence of PVT and any systemic VTE. The secondary endpoint was overall survival calculated from time of diagnosis. Univariate and multivariate logistic regression analyses were conducted to assess the association of PVT with a set of clinical covariates, and the survival curve was estimated using the method of Kaplan-Meier. Results: The mean age of the total population was 60.4 ± 11.9, and one-third of the patients underwent liver transplant. The incidence of PVT in the total population was 31% (60/194) with a higher incidence in the non-transplant group compared to transplanted patients (34% vs. 24%; p= 0.08). In univariate analysis, advanced stage, major vessel involvement, higher MELD score, higher Child-Turcotte-Pugh (CTP) classification, lower serum albumin, elevated serum bilirubin, elevated serum alpha-fetoprotein (AFP) level, and elevated INR were associated with development of PVT (p <0.05 for each). In multivariate analysis CTP class, stage, major vessel involvement, serum albumin, and serum AFP were independently and significantly associated with PVT (p <0.05 for each). The presence of PVT was associated with reduced survival (median survival 4.61 months for those with PVT versus 17.55 months for those without PVT, HR 2.01, p <0.001). The incidence of systemic VTE in the total population was 6.7%, and patients with PVT had a higher rate of systemic VTE compared to patients without PVT (11.5% vs. 4.4%; p 0.044). Conclusions: PVT is common in patients with HCC and is associated with worse outcomes. The correlation between PVT and systemic VTE suggests a common mechanism of hemostatic activation. Advanced stage, higher CTP class, major vessel involvement, and serum albumin and AFP levels are predictive of PVT. Identifying patients at high-risk for PVT and instituting prophylaxis may affect HCC outcomes. No significant financial relationships to disclose.
Phase II study of sequential chemotherapy with cisplatin (P) in combination with infusional 5FU/LV (PFL) followed by irinotecan (Ir) + 5FU/LV (IrFL) followed by docetaxel (T) + 5FU/LV (TFL) in patients (pts) with metastatic gastric carcinoma (MGC) by the Gruppo Oncologio Nord-Ovest (GONO)
Authors: Loupakis F. , Masi G. , Bursi S. , Picone V. , Mentuccia L. , Granetto C. , Fea E. , Murr R. , Antonuzzo A. , Falcone A. 
Published: March 2020

15059 Background: 5FU in combination with P can be considered a standard treatment for MGC. Ir and T are active agents with not complete cross-resistance with P and 5FU. The combination of Ir or T with P and 5FU is feasible but with substantial toxicities. A different way to include Ir and T in the first-line treatment of MGC is to use them sequentially to a P and 5FU containing regimen. Methods: we conducted a phase II study of first-line sequential chemotherapy in MGC pts with measurable disease (RECIST criteria). Treatment consisted of: 3 cycles of PFL (biweekly P 50 mg/sqm d1, LV 200 mg/sqm d1 and 5FU 3200 mg/sqm 48-h c.i. starting on d1) followed by 3 cycles of IrFL (biweekly Ir 180 mg/sqm d1 and 5FU/LV) followed by 3 cycles of TFL (biweekly T 50 mg/sqm d1 and 5FU/LV). Evaluation of disease was performed every 3 cycles. Results: 46 pts have been enrolled. Pts characteristics are: median age = 60 years (37–75), M/F = 36/10, sites of disease (single/multiple) 9/37, ECOG PS 0/1 = 27/19. Treatment was well tolerated. Grade 3–4 non-haematological toxicities were: diarrhea in 2,5% pts with PFL; diarrhea and asthenia in 2,5% and stomatitis in 5% pts with IrFL; stomatitis in 5,7% pts with TFL. Grade 3/4 neutropenia was observed in 14% pts with PFL, 15% with IrFL and 22,9% pts with TFL. Nor febrile neutropenia neither toxic deaths have occurred. Two pts had not evaluable disease and 6 are still receiving treatment. We observed 1 CR and 8 PR with PFL (RR 24%) among the 38 evaluable pts. IrFL improved responses in 10 pts while 4 pts progressed and TFL further improved responses in 6 pts while 5 pts progressed. Response rate at the end of the planned 9 cycles was 40% (4 CR, 11 PR; 95% CI 25–58%). At a median follow-up of 15.5 mos median TTP is 6.8 mos and median OS is 13.5 mos. Conclusions: this sequential treatment is feasible with a very favourable safety profile and produces encouraging results in terms of activity and efficacy in a population of unselected MGC patients. Final data will be presented at the meeting. Partially supported by A.R.C.O. Foundation. No significant financial relationships to disclose.
Lack of concordance between I-111 pentreotide (PEN) status and immuno-histochemistry (IHC) status for somatostatin receptors type 1, 2, and 3 in neuroendocrine tumors (NET)
Authors: Palhares A. C. , Costa F. P. , Belfer A. J. , Bacchi C. E. , Jokh S. H. , Hoff P. M. , Buzaid A. C. , Maluf F. C. , Marques R. J. , Dzik C. , Lopes L. F. 
Published: March 2020

15060 Background: The use of somatostatin analogues (ST) in the treatment of NET is recommended for functional and non- function slow progressing tumors that present with positive PEN. The goal of the study was to determine if expression of ST receptors type 2, 3 and 1 in NET tumors by IHC predict the PEN status and response to ST. Methods: Retrospective analysis of paraffin blocs from primary or metastatic sites and PEN imaging from 39 patients with a diagnosis of NET confirmed by independent pathology review. IHC analysis was performed in a central laboratory using antibody ST receptor type 1 from Neomarkers and type 2 and 3 from Affinity Bio Reagents. Status for each receptor type was reported as positive or negative, diffuse or focal and by % of positive cells. All slides were reviewed by the same pathologist. PEN images were submitted to an independent radiology review and reported as positive or negative and the signal intensity was graded from 1 to 4. Investigators were blinded to receptor and PEN status. This concordance analysis study was designed with a power to detect at least 60% correlation between receptor and PEN status with type I error of 5% and a type II error of 20%. Results: There was no correlation between receptor and PEN status ( Table ). Furthermore, there was no significant correlation between PEN and receptor types 3 and 1 in receptor type 2 negative patients (p=0,54, p=0,14, respectively). There was no correlation between receptor type status and PEN positive intensity. No independent or multivariate characteristics by IHC can correlate to PEN status in this cohort. Conclusions: Commonly used antibodies for IHC detection of receptors type 2, 3 and 1 used in this study failed to correlate with PEN. These results do not support the use of IHC as a substitute for PEN with respect to prediction of ST activity in NET. [Table: see text] No significant financial relationships to disclose.
Minimal residual local disease predicts improved survival after chemoradiotherapy in patients with squamous cell carcinoma of the esophagus
Authors: Rizk N. P. , Tang L. , Park B. J. , Flores R. , Venkatraman E. , Bains M. S. , Ilson D. , Minsky B. , Rusch V. W. 
Published: March 2020

15070 Background: Our recent analyses (JCO, in press) showed that residual nodal disease but not T-stage predicted survival after chemo-radiotherapy (CRT) and surgery for esophageal adenocarcinoma (AC). In this study, we investigated prognostic factors for esophageal squamous cell carcinoma (SCC) after CRT. Methods: Retrospective review of patients with esophageal SCC who had CRT and esophagectomy. Data collected: demographics, CRT details, pathologic findings, and survival. Statistical methods included recursive partitioning (RP) and Kaplan-Meier (KM) analyses. Results: Patients included in the study were treated between 1/1996 and 2/2006. Follow up was thru 5/06. 91 patients were appropriate for analysis. There were 56 men (61.5%) and 35 women (38.5%). 72 (79.1%) patients had clinical regional disease prior to treatment, while the rest had locally advanced disease. Median radiation dose was 5040 cGy, and 78 (85.7%) patients received cisplatin based chemotherapy. 49 (53.8%) patients had a complete local pathologic response (pCR), including 10/91 (10.9%) who had a pCR with residual nodal disease. 42 (46.2%) patients had residual local disease. RP analysis identified 3 prognostic groups: a) Group 1 (n=52), patients with minimal residual local disease (pCR & T1- regardless of nodal status), b) Group 2 (n=28), patients with residual T2 disease (N0 and N1) as well as patients with T3–4N0 disease, and c) Group 3 (n=11), patients with residual T3–4N1 disease. 3-year survival by KM analysis was 68.4% in group 1, 45.6% in group 2, and 0 % in group 3 (p<0.001). Conclusions: Unlike adenocarcinoma of the esophagus where residual nodal disease after CRT is the most significant predictor of survival, in SCC of the esophagus, the presence of minimal residual local disease after CRT, regardless of nodal status, predicts the best survival. The implications of these findings might include establishing different endpoints to assess response to treatment and prognostic criteria. No significant financial relationships to disclose.
Efficacy of preoperative radiochemotherapy in patients with locally advanced pancreatic carcinoma
Authors: Lind P. A. , Isaksson B. , Almström M. , Johnsson A. , Albiin N. , Byström P. , Permert J. 
Published: March 2020

15073 Background: The optimal care for patients with irresectable, non-metastatic pancreatic carcinoma (PAC) is debated. We treated 17 consecutive cases with preop radiochemotherapy (RCT) as a means for downstaging their tumors and compared outcome with 35 patients undergoing direct surgery for primarily resectable PAC during the same time period. Methods: The patients had biopsy proven, irresectable, non-metastatic PAC which engaged >50% of the circumference of a patent mesenteric/portal vein for a distance >2 cm and/or <50% of the circumference of a regional artery for <2 cm. The preop therapy included 2 courses of Xelox (oxaliplatin 130mg/m2 d1; capecitabine 1000mg/m2 X 2 d1–14 q 3 w) followed by 3-D conformal radiotherapy (50.4 Gy; 1.8 Gy fractions) with reduced Xelox (d1–5 q 1 w X 6). Results: 6 cases of RCT-related CTC Grade 3–4 non-hematologic side-effects were diagnosed. Sixteen patients completed the RCT and were rescanned with CT/reevaluated for surgery 4 weeks post-RCT. Five cases were diagnosed with new metastases to the liver. Eleven patients were accepted for surgery and 8 underwent a curative R0-resection. The median overall survival for the latter group was 29 mos, which compared favorably with our control group of patients undergoing direct surgery for primarily resectable PAC (median OS: 16 mos (P=0.02). RO- rate: 75%). Periop morbidity was similar in the two cohorts but the duration of surgery was longer (576 vs 477 min; P<0.05) and the op blood loss was greater (3288 vs 1460 ml; P<0.05) in the RCT-cohort. The 30-day mortality was zero in both cohorts. Conclusions: Preop RCT in fit patients with locally advanced PAC resulted in a high rate of curative resections and promising median survival in our treatment series. This trimodality approach merits further exploration in new studies, which are currently underway at our Department. No significant financial relationships to disclose.
Predictive value of chemotherapy-induced neutropenia for drug efficacy in advanced gastric carcinoma: Analysis of prospective nationwide survey
Authors: Yamanaka T. , Matsumoto S. , Teramukai S. , Ishiwata R. , Nagai Y. , Fukushima M. 
Published: March 2020

15075 Background: Myelosuppression that occurs during chemotherapy has been reported to be a predictor of better survival in patients with breast or lung carcinomas. We evaluated the prognostic implications of chemotherapy-induced neutropenia in advanced gastric cancer. Methods: Data obtained from a prospective nationwide survey of oral fluoropyrimidine S-1, performed in Japan between 1999 and 2000, were reviewed. Advanced gastric cancer patients with both adequate bone marrow function and no prior history of chemotherapy within 6 months before starting S-1 therapy were analyzed (N=1055). Chemotherapy-induced neutropenia was treated as a time-dependent covariate, and the hazard ratios [HRs] of death for experiencing neutropenia, compared with no such toxicity, were estimated using Cox regression model. Results: During treatment with S-1, a total of 293 (28%) patients had grade 1 or higher neutropenia. The adjusted HRs from a multivariate Cox model were 0.72 for patients with grade 1 neutropenia (95% confidence interval [CI] 0.54–0.95; P=0.0189), 0.63 for those with grade 2 neutropenia (95% CI 0.50–0.78; P<0.0001), and 0.71 for those with grade 3–4 neutropenia (95% CI 0.51–0.98; P=0.0388). Conclusions: The results of this study suggest that occurrence of neutropenia during chemotherapy is an independent predictor of better survival for advanced gastric cancer, while the absence of such toxicity indicates that the dosages of drugs are pharmacologically inadequate. Monitoring of neutropenia in patients who receive chemotherapy may contribute to improved drug efficacy and patient survival. No significant financial relationships to disclose.
Hyperfractionated radiotherapy and biliary stenting for unresectable biliary tract cancers: Useful baseline data adding chemotherapy
Authors: Nakazawa M. , Shibayama C. , Nakamura M. , Akahane K. , Tamada K. 
Published: March 2020

15079 Background: The morbidity and survival advantage treated with the combination of hyperfractionated radiotherapy (HF) and biliary stenting has not yet established for patients with unresectable biliary tract cancers. A prospective study was carried out using HF and metallic stent in consecutive patients over 10 years in a single institution. Methods: From 1993 to 2003, consecutive 162 pts (radical 74, postoperative 83, postoperative relapse 5) were treated with HF. Out of 74 radical cases, 71 pts (36 male/35 female; median age 70yrs, range 35–88) were analyzed except 3 cases (manifestation of liver metastasis 1, ascites 1, rejection of treatment 1). Primary sites were; extrahepatic bile duct 56, gall bladder 15. Bile cytology showed adenocarcinoma in every case. HF was administered twice daily by 10MV photon, using 2 portals (ant-post), 3 portals (ant-post-right lateral) or wedged pairs (ant-lateral) with relatively small radiation fields (PTV was CTV +1∼1.5cm). Fractional dose was 1.4Gy with the interfractional interval of 4.5 hrs to a total median dose of 59.8Gy. Endpoints were overall survival and acute and late complications. Results: 1) Obstructive jaundice was relieved before HF through endoscopic biliary drainage in 92.9% (66/71). Metallic stent was applied in 66.2%(47/71), before HF in 35.2% (25/71) and after HF in 31.0% (22/71). 2) Median survival was 8 months (1–90) and 5-year survival was 28%. Multivariate analysis showed total HF dose as a sole significant prognostic factor (p=0.0347). 3) Acute complication was observed mainly in digestive tract, i.e., Grade 1–2 symptoms (anorexia, nausea) in 50.7% (36/71). Late complications were Grade 1–2 gastritis in 9.9% (7/71), Grade 3 gastric ulcer in 2.8% (2/71) and cholangitis in 1.4% (1/71). Conclusions: HF combined with meticulous biliary drainage and stenting by G-I specialists for advanced biliary tract cancers demonstrated excellent pt’s quality of life with less serious morbidities. This modality would offer useful baseline data further with appropriate systemic chemotherapy. No significant financial relationships to disclose.
Cell-based breast cancer risk stratification based on DNA methylation in fine needle aspiration samples
Authors: Euhus D. , Bu D. , Milchgrub S. , Leitch A. M. , Lewis C. M. 
Published: March 2020

1508 Background: Tumor suppressor gene (TSG) methylation is identified in nearly all breast cancers, but rarely in histologically normal breast tissue from wonen unaffected with breast cancer. Its occurrence in high risk preneoplasia and in benign breast tissue adjacent to breast cancer suggests that it may represent a high risk field change that could be exploited for cell-based breast cancer risk stratification. Methods: TSG methylation was measured by quantitative methylation-specific real time PCR in 53 breast tumor fine needle aspiration (FNA) biopsies, 84 cellular random periareolar FNAs (RP-FNA) ipsilateral or contralateral to these cancers, 36 cellular RP- FNAs from unaffected women at high risk for breast cancer by the Gail model, and 95 cellular RP-FNAs from unaffected women at lower risk by the Gail model. Results: The breast tumors showed a high frequency of TSG methylation: RASSF1A 80%, HIN-1 65%, Cyclin D2 60%, RAR-β2 53%, and APC 47%. In general, RP-FNA samples from cancer patients and Gail high risk patients showed a greater frequency of methylation than samples from Gail lower risk patients: RASSF1A 43% vs. 21%, P = 0.001, HIN-1 32% vs. 20%, P = 0.05; Cyclin D2 18% vs. 9%, P = 0.10; RAR-β2 21% vs. 18%, P = 0.68; and APC 25% vs. 16%, P = 0.17. Twelve of 215 RP-FNA samples (5%) showed very high levels of methylation (>10% methylation for two or more genes). Only two of these samples were from women classified as lower risk by the Gail model. Methylation frequencies were entirely independent of cell yields but the frequency of RASSF1A methylation increased with increasing Masood scores (P = 0.05). Methylation of RASSF1A in one breast was highly predictive of RASSF1A methylation in the opposite breast (P < 0.0001). Conclusions: TSG methylation appears to be a breast cancer risk-associated field change that can be quantified in RP-FNA samples. RASSF1A methylation occurs frequently in benign breast epithelium, provides reasonable discrimination between high and lower risk breasts (O.R. = 2.0), is related to cytological atypia, and may be an early marker of a methylator phenotype. Quantification of TSG methylation in RP-FNA samples may provide a valuable surrogate endpoint biomarker for Phase II prevention trials. No significant financial relationships to disclose.
Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer: A single-center study
Authors: Boeck S. H. , Wilkowski R. , Bruns C. J. , Issels R. D. , Schulz C. , Moosmann N. , Laessig D. , Golf A. , Heinemann V. 
Published: March 2020

15085 Background: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem)-failure is defined in patients with advanced pancreatic cancer (PC). Methods: Within this study we prospectively collected clinical data of 37 patients (pts) with advanced PC who were treated with capecitabine (Cape) at our center. Cape was offered to patients who already had received at least one previous treatment regimen containing full-dose Gem (either as single- or combination chemotherapy or sequentially within a radio- chemotherapy (RCT) protocol), who presented with a KPS = 70% and had adequate organ function. Cape was administrated orally at a daily dose of 2 x 1250 mg/m2 for 14 consecutive days followed by 7 days of rest (in pts > 65 years: 2 x 1000 mg/m2/d). Treatment cycles were repeated every 3 weeks and continued until disease progression or unacceptable toxicity. Results: A median number of 3 treatment cycles (range 1–36) was given to 37 pts (54% male, median age 63 yrs, 97% with metastatic disease); 15 pts previously underwent RCT, 20 pts had received one previous treatment regimen and 17 pts 2 or more previous regimens. After a median follow- up of 6.1 months, 10 pts are still alive including 4 pts still on Cape. Currently, 35 pts are evaluable for response: no complete or partial response was observed, but 13 pts (37%) had stable disease (SD). A CA19–9 reduction > 20% after 8 weeks of Cape was determined in 6 pts (16%), all of them had SD. Median TTP was 2.2 months, median overall survival (since start of Cape treatment) was 7.5 months. Predominant grade 2 and 3 toxicities (per patient analysis) were: hand-foot-syndrome 30%, anemia 24%, diarrhea 14%, nausea/vomiting and leukopenia 11% each. One pt had a grade 3 infection, 1 pt experienced grade 4 cerebral ischemia during treatment with Cape. Conclusion: Single-agent Cape is a safe treatment option for Gem-pretreated pts with advanced PC. The disease control rate of 37% and a median TTP of 2.2 months appear interesting in this patient population. Further evaluation of Cape in controlled clinical trails is recommended in Gem-refractory pts with advanced PC. No significant financial relationships to disclose.