bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superiority of trimodality therapy to surgery alone in esophageal cancer: Results of CALGB 9781
Authors: Tepper J. E. , Krasna M. , Niedzwiecki D. , Hollis D. , Reed C. , Goldberg R. , Rich T. , Kiel K. , Mayer R. 
Published: March 2020

4012 Background: CALGB 9781 was a prospective randomized Intergroup trial of trimodality therapy versus surgery alone for the treatment of stages 1–3 esophageal cancer. Methods: Five-hundred patients were targeted for enrollment with three years of follow-up planned. The primary endpoint was overall survival. All patents had EGD with biopsy, barium esophagogram and CT. Additional staging by EUS and/or thoracoscopy/laparoscopy was recommended. Patients were randomized to treatment with either surgery alone or cisplatin (100mg/m2) and 5FU (1000 mg/m2/d × 4d) weeks 1 and 5 concurrent with radiation therapy (50.4 Gy- 1.8 Gy/fx over 5.6 weeks) followed by esophagectomy with lymph node dissection. Results: A total of 56 patients were entered on study between October 1997 and March 2000 when the trial was closed due to poor accrual. Thirty patients were randomized to trimodality therapy and 26 to surgery alone. Patient characteristics were similar between groups. Surgical staging was conducted in just over 50% of patients in both groups. The primary toxicities of Gr 3 or greater with preoperative therapy were hematopoietic (54%), and esophagitis/dysphagia (40%). There were 14 and 17 patients with surgical complications on the trimodality and surgery alone arms, respectively, with 2 post-surgical deaths (within 30 days), both on the surgery alone arm. Postoperative hospital stays were 11.5 and 10 days, respectively. Median follow-up is 6 years. An intent- to- treat analysis showed a median survival of 4.5 yrs vs 1.8 yrs in favor of trimodality therapy (log-rank p=0.02). A log rank test with stratifications by N stage, staging approach and histology demonstrated a p-value of 0.005. 5-year survival was 39% (95% CI [21%, 57%]) vs 16% (95% CI [5%, 33%]) in favor of trimodality therapy. Analysis of progression-free survival is underway. Conclusions: This randomized study demonstrates a long-term survival advantage with the use of chemoradiation therapy followed by surgery in the treatment of esophageal cancer. Although accrual was well below that planned, the observed survival difference is statistically significant and suggests that trimodality therapy is an appropriate standard of care for patients with this disease. No significant financial relationships to disclose.
Irinotecan/capecitabine versus cisplatin/capecitabine in advanced adenocarcinoma of the stomach or gastroesophageal junction: Interim analysis of a randomized German AIO phase II study
Authors: Moehler M. , Kanzler S. , Geissler M. , Raedle J. , Ebert M. , Scherubl H. , Flieger D. , Seufferlein T. , Galle P. R. , Hoehler T. 
Published: March 2020

4032 Background: Irinotecan with 5-FU is highly effective in advanced gastric cancer. In addition, capecitabine seems to be as effective as 5-FU, with its advantage of oral administration. Thus, we compared efficacy and toxicity of irinotecan/capecitabine versus cisplatin/capecitabine in this prospective multicentric, open trail. Methods: Patients (pts) with previously untreated locally advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction and Karnofsky Performance status (KPS) of ≥ 60%, at least one measurable lesion and adequate organ functions were eligible. Pts were randomized to 3-weekly cycles of irinotecan 250 mg/m2, day 1 (arm A) or to cisplatin 80 mg/m2, day 1 (arm B). Capecitabine was administered at a 1000 mg/m2 twice daily for 14 days followed by a 7-day rest in both arms. Primary endpoint was remission rate, treatment was continued until disease progression. Results: At time of abstract submission, 91 of 120 pts (planned sample size) were randomized to arm A (45 pts) or B (46 pts). Interim data were available on 76 patients included into intent to treat analysis (34 pts arm A, 42 pts arm B). Baseline characteristics (arm A vs. B) were median age: 60 vs. 64 years, gender (female/male) 23%/77% vs. 30%/70%, KPS (≥80%) 97% vs. 93%, tumor distribution of gastric origin and gastroesophageal junction 85%/15% vs. 63%/37%. Grade 3 toxicities in A/B (% of pts) were anemia 3/9, neutropenia 17/19, diarrhoea 17/5, nausea 14/21, vomiting 3/14, hand-foot syndrome 6/2, respectively. Grade 4 toxicity occured only for neutropenia with 3% vs.5% in A/B, respectively. In 59 evaluable pts (28/31 in A/B), overall remission rate (CR + PR) and tumor control rate (CR + PR + SD) were 39% vs. 42% and 64% vs. 74%, respectively. Despite being only very descriptive, median progression-free and overall survival (arm A vs B) were 5.2 vs. 5.0 and 8.9 vs. 9.4 months, respectively. Conclusions: In patients with locally advanced or metastatic gastric and gastroesophageal cancer, both regimen irinotecan/capecitabine or cisplatin/capecitabine are effective, well tolerated and can be administered safely on an out-patient basis. Currently, both treatment arms are comparable. Accrual continues. No significant financial relationships to disclose.
Pancreatectomy for neoplasm: National outcomes in mortality
Authors: McPhee J. T. , Zayaruzny M. , Whalen G. F. , Litwin D. E. , Sullivan M. E. , Anderson F. A. , Tseng J. F. 
Published: March 2020

4035 Background: Pancreatic resection remains the only potentially curative intervention for pancreatic cancer. The goal of this study was to evaluate factors affecting outcomes after pancreatectomy for neoplasm using a large national database. Methods: This is a retrospective analysis of 6,091patients (pts) undergoing pancreatic resection for non-endocrine neoplastic disease obtained from the National Inpatient Sample 1998–2003 (≈ 30,241 pts nationally by weighted analysis). Crude primary outcome measures of in-hospital mortality and postoperative disposition were analyzed by chi-square. A proportional hazards model was then constructed to adjust outcomes for age, sex, hospital teaching status, hospital surgical volume and selected co-morbid conditions. Results: 42,380 patient discharges (≈209,016 nationally) occurred with a primary diagnosis of pancreatic neoplasm. 6,091 (14%) pts underwent resection during that hospitalization. In-hospital mortality was 5.8% with a significant decrease of 7.7% - 4.4% from 1998–2003 (p=.016, regression coefficient .0042). In the univariate analysis pts treated at a non-teaching hospital had higher mortality rates (9.4% vs. 4.4% p<.0001). However, when adjusted for covariates including hospital surgical volume [low (<4 resections/year), medium (4–13/year), high (>13/year)] teaching status became insignificant in predicting mortality. Resections done at low and medium volume centers were predictive of higher mortality compared to high volume centers (OR 4.1 [2.7, 6.1] and OR 2.4 [1.6, 3.6]). Female gender was predictive of lower mortality (OR 0.58 [0.46, 0.74]). Younger pts (40–69) had lower mortality than pts 70 years or older. Overall, median post-operative length of stay (LOS) was 11 days (SD 23.9). LOS was shorter for female patients (median 10 days vs. ll days) and for resections done at high volume centers (median 10 days vs. ll days). Conclusions: This large observational study demonstrates an improvement in operative mortality for patients undergoing pancreatectomy for neoplastic disease 1998–2003. Furthermore, it demonstrates superior adjusted outcomes in terms of mortality, and LOS, for females, younger patients, and those treated at high volume surgical centers in the United States. No significant financial relationships to disclose.
Analysis of circulating biomarkers of sunitinib malate in patients with unresectable neuroendocrine tumors (NET): VEGF, IL-8, and soluble VEGF receptors 2 and 3
Authors: Bello C. , Deprimo S. E. , Friece C. , Smeraglia J. , Sherman L. , Tye L. , Baum C. , Meropol N. J. , Lenz H. , Kulke M. H. 
Published: March 2020

4045 Background: Sunitinib malate (SU11248) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity that specifically inhibits VEGFR, PDGFR, KIT, RET, and FLT3. In a phase II trial of 109 patients with metastatic neuroendocrine tumors (NET), sunitinib treatment was associated with ORR and high rates of SD in patients with carcinoid and pancreatic islet cell tumors (Kulke et al, ASCO 2005). To characterize potential biomarkers of biological response to sunitinib, we analyzed plasma levels of a panel of soluble proteins from patients in this trial. Methods: Patients received sunitinib in 6-week cycles comprised of 50 mg/day for 4 weeks followed by 2 weeks off treatment. Pre-dose plasma samples from 106 patients were obtained on days 1 and 28 of multiple cycles. Plasma levels of VEGF, soluble VEGF receptor 2 (sVEGFR-2), interleukin-8 (IL-8), and a novel biomarker, sVEGFR-3, were measured via ELISA analysis. Results: Plasma levels of each protein were frequently modulated during the course of treatment. At the end of cycle 1, VEGF levels were increased more than 3-fold over baseline in ∼50% of all patients. Average baseline VEGF levels were higher in the islet cell group (62 vs. 40 pg/ml, P = 0.06). In cycle 1, sVEGFR-2 and sVEGFR-3 levels were significantly decreased by ≥30% in ∼60% and 70% of all patients, respectively (P < 0.0001). Levels tended to return to near-baseline after 2 weeks off treatment. The reduction in sVEGFR-3 levels in cycle 1 was, on average, greater in the subset of patients with PR (n=11) compared to others (45% vs. 38%). Overall, there was a 2.2-fold average increase in IL-8 levels by the end of cycle 1, and a larger proportional increase in IL-8 levels in patients exhibiting decreases in tumor size, patients who also tended to have lower baseline IL-8 levels. Further analysis of correlations with pharmacokinetic and clinical parameters is ongoing. Conclusions: Our results suggest that this panel of circulating proteins may be of utility as pharmacodynamic biomarkers of sunitinib activity in patients with advanced NET. sVEGFR-3 may be a novel biomarker of the biological activity of sunitinib in NET, and IL-8 may be of particular interest as a potential predictor of response. [Table: see text]
Clinical effects of esophagectomy for patients 80 years of age and older with thoracic esophageal cancer
Authors: Morita M. , Nishida K. , Koga T. , Egashira A. , Tokunaga E. , Oki E. , Sadanaga N. , Kakeji Y. , Maehara Y. 
Published: March 2020

4049 Background: Esophageal cancer tends to mainly occur in elderly patients. Although a radical operation is the most effective existing therapy, the associated operative morbidity is still high. As a result, the indications for an esophagectomy in elderly patients (especially for patients over 80 years of age) remain controversial. Methods: A total of 599 patients with thoracic esophageal cancer who underwent an esophagectomy by the transthoracic approach since 1986 were evaluated. They were divided into 3 groups depending on age, namely groups I (<69 y.o., n = 441), II (70–79 y.o., n = 143) and III (≥80 y.o., n = 15). No significant differences were observed in the location of the tumor, histological type or stage. A distal esophagectomy with a left thoracotomy was performed for 40, 46, and 47% of the patients, respectively, while the others underwent a subtotal esophagectomy with a right thoracotomy. In group III, surgery was only done for cases with PS 0 or 1 as well as a normal cardiac and pulmonary function (ejection fraction ≥65 %, vital capacity ≥80 %, FEV 1.0% > 70%). Results: Postoperative complications occurred in 31 % of group I and 39 % of group II patients, and the incidence of pulmonary complication was 9 and 18 %, respectively (P < 0.01). In group III, the operative morbidity and mortality were 27 and 0 %, respectively, and pulmonary complications only occurred in one patient (7%). No significant difference was observed in the disease-free survival (DFS: 50, 46 and 58 % for 3yrs, 44, 40 and 33 % for 5 yrs), while the overall survival rates were worse in the older groups as a result of death due to causes other than recurrence (45, 34 and 34 % for 3yrs and 38, 26 and 9 % for 5 yrs in groups I, II and III, respectively. P < 0.01 group I v.s. II). Conclusions: An esophagectomy is considered to be a viable treatment alternative in patients over 80 years of age without increasing morbidity, when the indications for surgery are strictly determined. Furthermore, the DFS in these patients was similar to that observed in younger patients although the incidence of death due to causes other than cancer was found to be higher. An esophagectomy should therefore be considered as an effective treatment strategy even in elderly patients over 80 years of age. No significant financial relationships to disclose.
A phase II study of capecitabine plus oxaliplatin (XELOX) as first-line therapy for patients with advanced gastric cancer
Authors: Park Y. , Lee J. , Ryoo B. , Ryu M. , Yang S. , Kim B. , Shin D. , Chang H. , Kim T. , Kang Y. 
Published: March 2020

4079 Background: The combination chemotherapy of capecitabine and cisplatin showed considerable activity and good feasibility in patients with advanced gastric cancer. Oxaliplatin has a more favorable toxicity profile compared to cisplatin. The purpose of the study is to evaluate the efficacy and toxicity of capecitabine plus oxaliplatin combination chemotherapy in previously untreated patients with advanced gastric carcinoma. Methods: Patients received intravenous oxaliplatin 130 mg/m2 over 2 hours on day 1 plus oral capecitabine 1000 mg/m2 twice daily on days 1–14, every 3 weeks. Treatment was continued until progression of disease or intolerable toxicities with a maximum of 8 cycles. All the measurability and response evaluations were reviewed and confirmed by one investigator. Results: Total 54 patients were enrolled (37 men, 17 women). The median age was 57 years (range 29–70). Among these 54 patients, fifty-two patients were evaluable. A total 311 cycles of chemotherapy were delivered. The overall response rate was 63% (95% CI, 50–76%), with complete response in 2 patient and partial responses in 32 patients. After a median follow-up of 13 months, median progression-free survival was 5.8 months (95% CI, 4.4–7.2 months); median overall survival was 11.9 months (95% CI, 8.8–15.1 months). The treatment was generally well tolerated. The most common haematological adverse event was anaemia (70% of patients). Grade 3- 4 neutropenia was observed in 4 patients and neutropenic fever was experienced in only 1 patient. Four patients had G3 thrombocytopenia, which was accompanied by G3 gastrointestinal bleeding. The most common non-haematological toxicities were neuropathy (70%), vomiting (50%), diarrohea (33%), and hand-foot syndrome (39%). But, G3–4 toxicities were rare. There was one treatment related death which was associated with grade IV neutropenic sepsis. Conclusion: XELOX was active and well tolerated as a first-line therapy for advanced gastric carcinoma. No significant financial relationships to disclose.
Extended safety and efficacy data on S-1 plus cisplatin in patients with advanced gastric carcinoma in a multi-center phase II study
Authors: Lenz H. , Lee F. C. , Haller D. G. , Singh D. , Benson A. B. , Strumberg D. , Yanagihara R. H. , Yao J. C. , Phan A. T. , Ajani J. A. 
Published: March 2020

4083 Background: We obtained additional phase II safety and efficacy data in a multi-center setting on an active regimen of S-1 plus cisplatin; the experimental arm of the global phase III First-Line Advanced Gastric cancer Study (FLAGS). Methods: Eligible patients had untreated advanced gastric cancer (AGC), histologic proof, KPS ≥70%, adequate organ function, and gave written consent. Patients received S-1 (25mg/m2 p.o. bid on days 1–21) plus cisplatin (75mg/m2 i.v. on day 1) every 28 days. All reported confirmed overall response rate (C-ORR), response durations, and time-to-progression (TTP) are externally reviewed. Results: All 72 patients were assessed for safety and 64 for efficacy. The median age was 56 years and median KPS was 90%. Median no. of cycles was 4. C-ORR was 50% (95% CI, 37%-63%). Median duration of response is >6 months. At 6 months, only 35% of patients have had cancer progression. Median survival (n=72) is 10.5 months (95% CI, 9.3 to NR). At least one SAE occurred in 43% of patients. The frequent grade 3 or 4 adverse events (occurring in >10% of patients) included: fatigue/asthenia (26%), vomiting (21%), nausea (18%), diarrhea (17%), neutropenia (18%), anorexia (11%), and dehydration (11%). Febrile neutropenia (1.4%) and grade 4 diarrhea (1.4%) were rare. Conclusions: These extended data confirm that S-1 plus cisplatin has a very desirable safety profile and impressive efficacy data in AGC. FLAGS will complete accrual of >700 patients by March of 2007. (Supported by Taiho Pharma-USA). [Table: see text]
Evaluation of significance of endoscopic mucosal resection (EMR) in early esophageal cancer
Authors: Yoshii T. , Tamai S. , Motohashi O. , Yonemitsu K. , Kiyohashi A. , Takagi S. , Nakayama N. , Murata Y. 
Published: March 2020

4088 Background: Radical surgery for esophageal cancer is very invasive. Endoscopic mucosal resection (EMR), which conserves the esophagus, is a minimally invasive and attractive therapeutic modality for early stage esophageal cancer. However, when the tumor reaches the deep mucosal or submucosal layer (“T1b” according to TNM classification), the incidence of lymph node metastasis (LNM) increases up to 10–50%. Therefore, the indications of EMR have to be clarified. Methods: Retrospective analysis was performed regarding the clinical course of 41 patients who were diagnosed as having cT1bN0M0 esophageal cancer and underwent EMR between 1994 and 2004 at our hospital. Statistical analysis was performed by the log-rank and Kaplan-Meier methods. Results: Thirty nine patients were selected and followed up without any additional therapy after obtaining written informed consent. Twenty patients (51%) had multiple primary cancers, 10 died, and 29 are still alive. MST of the dead patients was 22 months, and 7 of them (70%) died of advanced multiple primary cancers, while death was cause specific in only one case (due to LNM). The survival curves showed no significant differences between the patients with early multiple primary cancers and those without multiple cancers patients (MST = 72 months, p < 0.7784). In most of the dead patients and 23 of the surviving patients, the local lesion was well controlled without any recurrence. Conclusions: Many patients with early esophageal cancer who underwent EMR tended to die of multiple primary cancers. When the patient had early multiple primary cancers, the prognosis was not different from those without such cancer and the local lesion was well controlled. We concluded that EMR is a very useful therapeutic modality for local control as it is minimally invasive, especially in patients with multiple primary cancers. No significant financial relationships to disclose.
Surgical resection for pancreatic cancer: Correlates of margin positivity
Authors: Ashraf S. , Andrews C. , Kuvshinoff B. , Pande A. , Javle M. , Gibbs J. F. 
Published: March 2020

4097 Background: Positive surgical margins (PSMs) occur in 20–40% of pancreatic cancer cases treated surgically. PSMs are associated with local recurrence and poor survival. Objectives: Correlate clinicopathological parameters with PSMs in pancreatic cancer patients (pts) undergoing surgical resection. Methods: Clinicopathological data for 71 pts who underwent surgical resection for pancreatic cancer from 1999–2005 were obtained. Data including location, AJCC stage, tumor size, type of resection, use of neoadjuvant therapy, grade, morphology, perineural and angiolymphatic invasion were correlated with PSMs and survival using logistic regression, Fisher-exact test and log-rank test. Results: There were 29 males; median age was 65 years and median follow-up 14 months. Histologies were: adenocarcinoma (n = 67), sarcomatoid (n = 2), adenosquamous (n = 1) and mucinous cystadenocarcinoma (n = 1). Sites of disease were: head only (n = 56), head/uncinate (n = 7) and body/tail (n = 8). Surgical treatments included Whipple (n = 43), pylorus preserving Whipple (n = 18) distal pancreatectomy (n = 8) and total pancreatectomy (n = 2). Pathological AJCC stages were: ΙA (n = 4), ΙB (n = 2), ΙΙA (n = 14), ΙΙB (n = 48), and ΙΙΙ (n = 3). Neoadjuvant chemoradiation (CRT) was administered in 10 cases; 38 other pts received postoperative adjuvant therapy including CRT (n = 36)/chemotherapy only (n = 2). Overall median survival was 30 months and disease free survival 18.6 months. Nineteen cases (27%) had PSMs. PSMs were pancreatic transection line (n = 11), retroperitoneal margin (n = 9), bile duct (n = 1) and peripancreatic soft tissue (n = 2). On univariate analysis, PSM was associated with advanced AJCC stage (p = 0.02) and tumor location other than pancreatic head (p = 0.02). PSM rate was 10% (1/10) and 31% (18/61) for pts with/without neoadjuvant therapy, respectively (p = 0.27). On multivariate analysis, PSM correlated with AJCC stage (p = 0.04) and tumor location (p = 0.05). PSMs were not significantly related to survival or recurrence (p = 0.09). Conclusions: Advanced AJCC stage and tumor in pancreatic body/tail or uncinate are associated with PSMs following pancreatic cancer resection. Strategies to “downstage” with novel therapies prior to surgery should be investigated to facilitate a complete surgical resection. [Table: see text]
The PACT trial: Interim results of a randomized trial of TNFerade biologic plus chemoradiation (CRT) compared to CRT alone in locally advanced pancreatic cancer (LAPC)
Authors: Senzer N. , Rosemurgy A. , Javle M. , Reid T. , Posner M. C. , Chang K. J. , Owens M. , Shirinian M. , Stephenson J. , Hecht J. R. 
Published: March 2020

4102 Background: TNFerade is a second-generation replication-deficient adenovector, carrying the transgene encoding human TNF-α, regulated by the stress-inducible promoter Egr-1. In a phase I trial of TNFerade + radiation in 36 patients with advanced or refractory solid tumors, a 47% objective tumor response rate was observed, including 100% complete responses in 3 stage 4 melanoma patients, with 2/3 disease-free at >3.5 years. Methods: This controlled phase II trial randomizes 74 patients with newly diagnosed unresectable LAPC to 5-wks of TNFerade (4 × 1011 pu via weekly intratumoral injection) + CRT (5-FU [200 mg/m2/day CIV × 5 days/wk] and 50.4 Gy radiation) or CRT alone. All patients receive maintenance gemcitabine. Endpoints: Progression-free survival, safety, radiographic tumor response, CA 19–9 and survival. Results: In dose escalation (n=50) dose-limiting toxicities occurred in 3 patients at 1 × 1012 pu (pancreatitis in 2 and biliary obstruction), setting the MTD at 4 × 1011 pu. Compared with the first two cohorts (n=30), the MTD (n = 11) was associated with greater locoregional control and progression-free survival, a higher rate of stable or decreasing CA 19–9, improved overall survival (median = 11.2), and a high (45%) resection rate. Accrual continues in the randomized phase of the study at 20+ centers. The most frequent adverse events in the first 16 enrolled patients have been nausea (75%), abdominal pain (63%), constipation (50%), anemia (38%), diarrhea (38%), vomiting (38%), and weight loss (38%), with no significant difference in severity or frequency between the TNFerade + CRT and CRT groups. No thromboembolic events have been reported. Serum TNF-alpha levels have remained low (peak = 45.3 pg/mL, in a CRT patient). CA 19–9 has been stable (no change > 100 U/mL) or decreased in all but one CRT patient. Conclusions: These initial data indicate that TNFerade plus CRT, given as weekly intratumoral injections to patients with LAPC, is feasible and tolerable compared to CRT alone. With continued accrual, comparative tumor response and toxicity data will be available and updated. No significant financial relationships to disclose.