bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative induction chemotherapy with docetaxel-cisplatin followed by concurrent docetaxel-cisplatin and radiation therapy in patients with locally advanced esophageal cancer: A prospective, multicenter phase ll trial of the Swiss Group for Clinical Cancer Research
Authors: Ruhstaller T. , Widmer L. , Balmer Majno S. , Mingrone W. , Hess V. , von Moos R. , Borner M. , Schnider A. , Koeberle D. , Popescu R. 
Published: March 2020

4562 Background: The role of preoperative therapy in patients (pts) with locally advanced esophageal cancer remains unclear. Non-randomized and randomized studies were often performed in single and highly specialized centers. The purpose of this study was to investigate 1) the efficacy and toxicity of preoperative docetaxel-cisplatin together with radiation therapy (RT) 2) the feasibility of a complex preoperative strategy in a community-based multicenter setting. Methods: Eligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus or gastroesophageal junction (Siewert type l); staged by EUS, CT and PET scan; age 18–70y; PS <2; normal organ functions. Treatment: 2 cycles of docetaxel 75mg/m2 and cisplatin 75mg/m2 q3w, followed by weekly x5 docetaxel 20mg/m2 and cisplatin 25mg/m2 with concomitant 45 Gy RT in 25 fractions; surgery 3- 8 weeks after RT. A two stage-design was used with two primary endpoints: 1) efficacy (TRG : tumor regression grade ); 2) feasibility (successful completion of entire therapy and being alive 30 days after surgery). Results: 66 pts, 56 males, were included from 11 institutions; median age 61y (35–70y); AC 53%; SCC 46%; 53 pts (80%) completed the preoperative therapy, underwent resection and were alive 30 days after surgery; 10 pts (15%) had no resection (4 progressive disease, 4 medical reasons, 2 patient’s refusal). Of 56 (85%) pts who had surgery, 51 pts had RO-resection (91%), 5 pts (9%) died due to complications after surgery (3 after > 30 days). Conclusion: Our trimodality treatment shows encouraging antineoplastic activity with 57% histopathological responders (TRG1 and 2) and acceptable feasibility in a community-based multicenter setting. [Table: see text] No significant financial relationships to disclose.
Molecular signature of esophageal adenocarcinoma derived from microarray analysis of paraffin-embedded specimens predicts systemic recurrence following resection
Authors: Oh D. S. , Cooc J. , DeMeester S. R. , Mori R. , Kuramochi H. , Rizzetto C. , Danenberg K. , Danenberg P. , Hagen J. A. , Harpole D. H. , DeMeester T. R. 
Published: March 2020

4563 Introduction: Surveillance endoscopy in patients with Barrett’s esophagus has resulted in the diagnosis of an increasing number of early-stage adenocarcinomas. Surgical resection alone is curative in the majority of these patients, yet some will succumb to systemic disease. We hypothesize that among patients with early esophageal adenocarcinoma, there are distinct molecular signatures of tumors that are associated with systemic recurrence and those that are cured with resection alone. Methods: From a total of 36 patients with early-stage adenocarcinoma (T1–3, less than or equal to 4 involved nodes), 20 who were alive and without recurrence at a median follow-up of 61 months after resection alone were compared by microarray analysis with similar stage tumors from 16 patients that developed systemic disease and died at a median of 13 months after esophagectomy. Following microdissection of paraffin-embedded specimens, RNA was isolated, amplified, labeled, and hybridized to Affymetrix U133 Plus 2.0 GeneChips. Results: A T-test with unequal variance assumption identified 328 differentially expressed probe sets (false discovery rate <0.05; p67 mos. vs. 13 mos., respectively; p<0.001). Significant canonical pathway deregulation between long and short survivors included GABA receptor, PDGF, PPAR, IL-6 signaling, oxidative phosphorylation and the pentose phosphate pathway. Conclusion: The molecular signature of early-stage esophageal adenocarcinomas may be able to distinguish patients at increased risk for the development of systemic disease and thereby guide use of adjuvant therapy and the intensity of follow-up. Confirmation of these findings in additional patients should prompt a prospective clinical trial. [Table: see text]
Chemoimmunotherapy with 5-fluouracil, leucovorin and interferon alpha-2b as adjuvant therapy after surgery in Gastric Carcinoma patients
Authors: Gonzalez H. A. , Londoño H. , Quiroz J. , Parra A. , Ramirez A. , González M. , Rodríguez A. , Varón C. , Romero N. 
Published: March 2020

4581 Background: The main treatment of Gastric Carcinoma(GC) is Surgery, but 5 years recurrence risk is 70% and mortality 50%. So that, effective adyuvant therapy, like chemotherapy, is needed to impact on survival ; results, however have been inconsistent at best. Inmunotherapy with interferon alpha, in gastric carcinoma, has only been employed in metastatic disease. The objective of this study was evaluate chemoimmmunotherapy role of interferon alpha - 2b,5-FU and LCV as adjuvant therapy in GC Methods: This is a randomized prospective study. Beginning 2/Oct /97 and finalizing 31/march/2005. Patiens with gastric adenocarcinoma, clinical stages II, III and non metastatic IV, after gastrectomy, without cancer antecedent were included. Treatment groups were assigned at random: Group A: 5-FU: 400 mg/m2, days (1–3), leucovorin: 50 mg. days (1–3), interferon alpha - 2b: 5x10^6 units sq, every other day, days (1–15). Group B: 5-FU, LCV without interferon alpha, at the same doses. Nine (9) monthly cycles were aplied. Clinical and paraclinical follow up was made appropriately. Statistic analysis was performed by Kaplan Meier method. Results: 52 patients were studied, 25 in group A and 27 in group B. Both of them had similar characteristics in median age, sex, histology, differentiation grade, gastric location, clinical stage: A: II: 28%, III: 72% (IIIB: 56%). B: II: 29,6%, III: 70% (IIIB: 55%).General survival (SG) analysis: Mean SG (%): A: 64%. B: 18,5%. Mean SG (months): A: 68,5 m. (CI 95%: 59–78,15). B: 27,98 ( CI 95%: 18,92–37,04). Survival curves comparison, minimum until 5 years: Log Rank, Breslow, Tarone Ware: P<0,00001, all of them in favor to group A. Mortality: Total:31/52: 59,6%. A: 36%. B: 81,48% (P<0,05). Disease free survival (DFS) analysis: Mean DFS (%): A: 52%. B: 18, 52%. Mean DFS(months): A: 58,85m (CI 95%: 47,4–70.3). B: 24,98m (CI 95 %: 15,3–34.6). DFS curves comparison: Log Rank: 0,0008. Breslow: 0,0003. Tarone Ware: 0,0004. All of them in favor to group A. Recurrence (%): Total: 34/52:65%. A: 48%. B: 81,48% ( P <0,05). Conclusions: This is the first study of adjuvant chemoimmunotherapy (CI) that includes interferon alpha - 2b in GC. This study shows CI with 5-FU, LCV and interferon alpha -2b is effective as adjuvant treatment in GC. No significant financial relationships to disclose.
Phase I study of stereotactic radiotherapy for unresectable hepatobiliary cancer and liver metastases
Authors: Dawson L. A. , Tse R. , Kim J. , Dinniwell R. , Lockwood G. , Sherman M. , Knox J. J. , Gallinger S. 
Published: March 2020

4590 Background: Safety of stereotactic radiotherapy (SRT) for unresectable hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CC) and liver metastases (LM) has not been well established. Results from a phase I study of 6 fraction SRT are reported. Methods: Eligible patients had unresectable or medically inoperable HCC, CC or LM, liver enzymes < 6 fold higher than normal, platelets > 80,000 bil/L, Child score A, > 800 cc uninvolved liver, KPS = 60 and unsuitability for standard therapies. Patients were treated with breath hold and image guided 6 fraction SRT. Dose was individualized to maintain the same risk of liver toxicity at three risk levels (I-5%, II-10%, III-20%). Escalation to level II and III occurred once at least 3 patients had been followed for >3 months without dose limiting toxicity (grade 4/5 < 1 month or grade 4/5 liver < 3 months) for each stratum. Stratification was based on diagnosis and liver volume irradiated (low <20%, mid 20–50%, high 50–80%). Results: From Aug. 2003 to Dec. 2006, 82 patients initiated SRT. Two patients discontinued SRT after 1 fraction for progressive disease (LM) and a variceal bleed (HCC). 80 patients completed SRT (38 LM, 32 HCC, 10 CC). Median age was 64 years (38–92 years). Median tumor volume was 293 cc (3–3088 cc). 24 patients (30%) had extra-hepatic disease. 17 HCC patients had portal vein thrombosis (53%), 14 HBV, 12 HCV and 4 alcoholic cirrhosis. The median prescribed dose was 40 Gy (24 Gy - 60 Gy) in 6 fractions. Within 3 months post SRT, no dose-limiting grade 4/5 toxicity or classic radiation liver toxicity was observed. Grade 3 liver enzymes (2 new, 9 pre-existing), thrombocytopenia (3), nausea (3) and fatigue (1) was observed. Child score declined in 8 patients (5 HCC, 2 CC, 1 LM), 6 with progressive disease. Late toxicity included 1 tumor-duodenal fistula, 1 bowel obstruction and 2 GI bleeds. The in-field response rate was 60% (LM 57%, CC 50%, HCC 67%): CR 14%, PR 46%, SD 23%, PD 17%. Actuarial 12 month local control was 78% (95% CI: 58- 90%). The median survival for LM, CC and HCC was 16.6 months (7.9–25.6), 13.1 months (6.0–28.4) and 11.0 months (8.6–20.8) respectively. Conclusions: Individualized SRT is a safe, promising treatment for unresectable liver cancer. No significant financial relationships to disclose.
Phase I/II trial of preoperative oxaliplatin, docetaxel, capecitabine, and radiation for localized esophageal cancer
Authors: Meluch A. A. , Spigel D. R. , Greco F. A. , Yardley D. A. , Burris H. A. , Farley C. , Peyton J. D. , Shipley D. L. , Steis R. G. , Hainsworth J. D. 
Published: March 2020

4595 Background: Preoperative chemoradiotherapy is a primary treatment option for patients (pts) with resectable esophageal cancer. Combination regimens using newer agents may improve pt outcomes. This multicenter community-based trial examined a modern triplet regimen comprised of oxaliplatin (O), docetaxel (D), and capecitabine (C) combined with radiation (RT). Methods: The primary endpoints were objective response rate (ORR) and safety. Eligibility criteria: pts with resectable stage I-III cancer of the mid-/distal-esophagus or gastroesophageal junction, measurable disease, ECOG PS 0–1, and informed consent. Treatment: O 40 mg/m2 IV and D 20 mg/m2 IV weekly x 5; C 1,000 mg/m2 PO twice daily D1–7, 15–21, 29–35; and concurrent RT to 45 Gy. Pts were resected 4–8 weeks later. O/D/RT safety was determined in a phase I portion (n=10) before adding C in a phase II portion. Results: 43 pts were enrolled from 9/04 to 12/06 (trial ongoing, n=60 planned). Data on 38 pts are available for analysis. Baseline characteristics: median age 61 years; male/female, 76%/24%; ECOG PS 0/1, 32%/68%; adenocarcinoma/squamous, 74%/26%; and stage I, II, III, 8%/45%/47%. The ORR was 58% (95% CI 42%-72%), with 4 complete and 18 partial responses. 37% had stable disease, and 1 pt had progressive disease (PD). 26 pts (68%) were resected. Unresected pts: awaiting surgery, 3 pts; poor PS, 4 pts; PD, 1 pt; pt choice, 1 pt; death, 3 pts. Pathologic complete responses were seen in 17 pts (65%). With a median follow-up of 16 months, 1-year progression-free survival (PFS) and overall survival (OS) are 58% and 64%, respectively. Median PFS and OS have not been reached. Grade (G) 3/4 non-hematologic toxicity: anorexia (21%), dehydration, esophagitis (16% each), nausea (13%), and dysphagia, fatigue, vomiting, and pain (11% each). Other G3/4 non- hematologic toxicities were = 5%. No G3/4 hematologic toxicities or treatment-related deaths occurred. Conclusions: O/D/C/RT appears safe and active as a preoperative regimen for resectable esophageal cancer - with a G3/4 esophagitis rate that compares favorably with historical combination regimens. Additional accrual and follow-up are needed to determine if these benefits are sustained. No significant financial relationships to disclose.
Detection and significance of circulating tumor cells (CTC) in patients with metastatic pancreatic cancer (PC) receiving systemic therapy
Authors: Ko A. H. , Scott J. , Tempero M. A. , Park J. W. 
Published: March 2020

4596 Background: Detection of CTC in the peripheral circulation of pts with solid tumors may provide useful prognostic and predictive information. In a previously reported pilot study, we detected CTC in approx 2/3rds of pts with all stages of PC using a flow cytometric-based approach. This study examines the significance of CTC using two separate methods in pts with metastatic PC undergoing systemic rx. Methods: Blood was obtained at baseline and after 2 months of rx from pts with metastatic PC participating in a phase II trial of gemcitabine, cisplatin, and bevacizumab. Two methods for measuring CTC were tested: immunomagnetic capture/flow cytometry (IC/FC) using anti-EpCAM Abs, and the Veridex CellSearch system. Wilcoxon Rank tests were used to test the association of CTC concentration at each time point, and change in concentration over time, with overall survival, time to tumor progression, and CA19–9 response. Results: CTC were measured in 48 indiv pts at baseline (31 using IC/FC, 23 using CellSearch, 6 using both methods) and in 39 indiv pts after 2 months of rx (20 IC/FC, 23 CellSearch, 4 both methods). No correlation was found between CTC concentration at either baseline or at 2 mos and any clinical endpoints (see table ). This was true for both IC/FC and CellSearch methods. 25 pts had serial CTC measurements using consistent methods at both time points (17 IC/FC, 12 CellSearch, 4 both methods). CTC concentration decreased in 9 of 17 pts (52.9%) tested by IC/FC and in 5 of 12 pts (41.7%) tested by CellSearch; however, change in CTC concentration over time was not associated with clinical outcomes. Too few pts have been tested by both methods at a given time point to establish a significant correlation betw the two methods. Conclusions: CTC can be detected in pts with metastatic PC using both methods tested in this study, albeit at low concentrations. The small sample size to date precludes our ability to determine the prognostic and predictive significance of these cells in this disease setting. [Table: see text] No significant financial relationships to disclose.
Curcumin and pancreatic cancer: Phase II clinical trial experience
Authors: Dhillon N. , Aggarwal B. B. , Newman R. A. , Wolff R. A. , Kunnumakkara A. B. , Abbruzzese J. L. , Hong D. S. , Camacho L. H. , Ng C. , Kurzrock R. 
Published: March 2020

4599 Background: Pancreatic cancer is virtually always lethal, and the only FDA-approved therapies–gemcitabine and erlotinib–produce objective responses in less than 10% of patients. Curcumin (diferuloyl methane) is a plant-derived dietary ingredient that suppresses NF-κB and numerous other pathways relevant to pancreatic cancer and has potent preclinical anti-tumor activity. Herein, we evaluated the safety and potential antitumor activity of curcumin against advanced pancreatic cancer, and its impact on biologic correlates. Methods: Patients received 8 grams of curcumin by mouth daily for two months and were then restaged. Maintenance therapy was continued at the same dose and schedule until disease progression. Results: Twenty-five patients were enrolled as of the date of analysis, with 21 evaluable for response. Circulating curcumin was detectable, albeit at low steady-state levels (about 31 ng/ml), suggesting poor oral bioavailability. To date, two patients have had prolonged stable disease (8 and 12+ months). Interestingly, one patient had a brief, but marked tumor regression (73%) (accompanied by significant increases (4–35-fold) in serum cytokine (interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1RA) levels). No toxicities have been observed. Curcumin down-regulated expression of NF-κB, COX-2 and phosphorylated STAT3 in peripheral blood mononuclear cells (PBMC) from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers)although the decrease did not reach statistical significance for p65. Curcumin was determined in patient plasma samples after enzymatic digestion with glucuronidase enzyme. While there was considerable variation in plasma curcumin levels from patient to patient, drug levels peaked at 22–41 ng/ml and remained relatively constant over the entire 4 week experimental period. Conclusions: We conclude that oral curcumin is well tolerated and, despite its limited absorption, has biologic activity in patients with pancreatic cancer. [Table: see text] No significant financial relationships to disclose.
Sunitinib as second-line treatment for advanced gastric cancer: preliminary results from a phase II study
Authors: Bang Y. , Kang Y. , Kang W. , Boku N. , Chung H. , Lanzalone S. , Lechuga M. J. , Sherman L. , Chao R. , Sobrero A. 
Published: March 2020

4603 Background: Sunitinib malate (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, approved internationally for the treatment of advanced RCC and imatinib-resistant or -intolerant GIST. We investigated the safety and activity of SU monotherapy in pts with previously-treated gastric cancer. Preliminary results from this open-label, multicenter, phase II study are reported. Methods: Eligibility criteria included measurable stage IV disease; 1 prior chemotherapy regimen; and ECOG PS =1. Pts took SU 50 mg/day for 4 wks followed by 2 wks off treatment in 6-wk cycles. A Simon 2-stage design was used with a target accrual of 38 pts in the first stage, expanding to 63 pts if =2 partial responses (PRs) were observed. The primary endpoint was RECIST-defined objective response rate. Secondary endpoints included duration of response and safety. Pharmacokinetic (PK) Ctrough parameters were also monitored. Results: As of Sept 15 2006, 38 evaluable pts (median age 56 years [range 29–78]; 2–3 metastatic sites [63%]; prior treatment with 5-FU ± platinum [P] [24%], capecitabine ± P [13%], TS-1 ± P [26%], other [37%]) have received a median of 2 SU cycles (range 1–3). Of 21 pts evaluable for efficacy, 1 PR has been confirmed and 8 pts had stable disease (SD), 4 with SD for =2 cycles. The most commonly reported AEs were typically grade 1/2 in severity and included stomatitis, skin discoloration, fatigue, anorexia, diarrhea, hand-foot syndrome (HFS), nausea and vomiting. Grade 3/4 toxicities included HFS (10.5%), fatigue (7.9%), anorexia (7.9%) and mucosal inflammation (5.3%). Grade 3/4 hematologic toxicities included neutropenia (29%), thrombocytopenia (29%) and anemia (11%). 7 pts experienced serious SU- related AEs requiring dose modifications in 3 pts and treatment discontinuation in 1 pt. Preliminary PK investigations indicate that concentrations seen in gastric pts are similar to those seen in other pts treated with SU. Conclusions: These initial findings show that SU is generally well tolerated and may have single-agent antitumor activity in pre-treated gastric cancer pts. Further trials with SU in combination with standard chemotherapy regimens are planned. No significant financial relationships to disclose.
Combination of gefitinib, cisplatin and 5-FU chemotherapy, and radiation therapy (RT) in newly-diagnosed patients with esophageal carcinoma
Authors: Sunpaweravong P. , Sunpaweravong S. , Sangthawan D. , Puttawibul P. , Mitarnun W. 
Published: March 2020

4605 Background: Efficacy of chemotherapy and RT in patients with esophageal carcinoma has been established in addition to surgical treatment. EGFR protein expression is prevalent in esophageal carcinoma; adding gefitinib to chemoradiotherapy may improve treatment outcome in this less favorable cancer. Methods: In this phase II study, untreated ECOG PS 0–2 patients with stage 2–4 esophageal carcinoma were recruited. Stage 2–4a patients were given gefitinib in combination with concurrent chemoradiation whereas stage 4b patients received only gefitinib and chemotherapy. Gefitinib 250 mg was taken daily in combination with cisplatin 80 mg/m2 D1 and 5-FU 1,000 mg/m2, 24 hour CI, D1–5 every 3 weeks to the maximum of 6 cycles. Concurrently with chemotherapy, stage 2–4a patients received RT, 2 Gy single daily dose to the total of 60 Gy. After a cohort of 10 patients, initial daily chemotherapy dose was reduced to cisplatin 65 mg/m2 and 5- FU 800 mg/m2 in pts who received concurrent RT due to gr 3–4 neutropenia and mucositis. Results: Thirty-seven patients, 33 esophageal squamous cell carcinoma (ESCC) and 4 adenocarcinoma (EAC) were accrued between August 2005 and November 2006. Twenty- seven patients were stage 2–4a and 10 patients were stage 4b. Twenty-five (93%) stage 2–4a patients completed chemoradiation. In stage 2–4a patients, 4 (15%) CR, 17 (63%) PR, 3 (11%) SD, and 3 (11%) PD were achieved. Four (15%) stage 2–4a patients thereafter underwent esophagectomy and 1 (25%) achieved pathological complete response. In stage 4b patients, 5 (50%) PR, 3 (30%) SD, and 2 (20%) PD were observed. Twenty-three (62%) ESCC responded whereas 3 (75%) EAC did. Major grade 3–4 toxicities included neutropenia (19%), leukopenia (19%), and anemia (16%). Diarrhea occurred in 70%, dry skin in 30%, mucositis/esophagitis in 27%, and rash in 14% of patients, mostly grade 1- 2. One patient had a chemotherapy-related death due to neutropenic septicemia. Conclusions: This combined EGFR inhibitor and chemoradiation regimen was feasible and efficacious in patients with newly-diagnosed esophageal carcinoma. Further investigation in Phase III trial is encouraged to better assess the benefit of this approach in comparison to conventional treatment. No significant financial relationships to disclose.