bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative or postoperative therapy for resectable gallbladder cancer? A retrospective analysis of patients treated at a single institution.
Authors: Siripurapu V. , Watson J. C. , Chun Y. S. , Gumbs A. , Hoffman J. P. 
Published: February 2017

309 Background: Gallbladder cancer (GBC) is the most common malignancy of the biliary tract. Less than 30% present at an early stage where surgical resection is curative. We examine a cohort of patients with GBC toward determining if preoperative and postoperative treatment of locally advanced GBC demonstrate any differing results in complications or survival. Methods: A retrospective review of patients seen at FCCC with GBC from Jan 1991 to Nov 2008 was performed. Demographics, clinical stage, surgical procedure, AJCC 7th stage, details of neoadjuvant and adjuvant treatment and complications of surgery were analyzed. Results: Fifty-one patients with GBC were identified. Of these, 66% had their GBC found incidentally, 77% had stage 2 or greater cancers, and 35 patients needed liver resection with portal lymphadenectomy. 13 patients had an extrahepatic bile duct resection. 10 patients had extended resections including pancreatoduodenectomy (5) or colectomy (5), while 6 had cholecystectomy alone. 25% (n=13) of the population had preoperative chemoradiation only, 30 % (n=15) had postoperative chemoradiation only, while 15% (n=8) received maintenance chemotherapy only. 10% (n=5) had preoperative and postoperative therapy, while twenty percent of the group (n=10) had surgery only. 49% had recurrences (n=25), with 48% percent of these being local-regional. Median survival was 30 months for the whole group, with 54.6 month median survival for the 41 patients without extended resection. No significant difference in survival was seen comparing preoperative therapy versus postoperative treatment (p=0.13). Five-year survival is 47% for those with minor hepatic resection compared to 25% for those with combined hepatic and colon or pancreatic resection. Conclusions: We present a retrospective view of patients treated in our center, the majority of whom received either preoperative or postoperative adjuvant therapy, both of which had good median survival and acceptable morbidity and mortality. Given the poor survival and high recurrence rate for stage II and greater cancers, we suggest that preoperative or postoperative adjuvant therapy for these cases may be equally effective. No significant financial relationships to disclose.
A phase II study of lapatinib and capecitabine in first-line treatment of metastatic pancreatic cancer (ICORG 08- 39).
Authors: McDermott R. S. , Calvert P. , Parker M. , Webb G. , Moulton B. , McCaffrey J. ,   Irish Clinical Oncology Research Group
Published: February 2017

315 Background: The combination of capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer patients has proved beneficial in terms of median survival duration, objective radiological response rate and decrease in tumour marker levels from baseline. In the phase I study of capecitabine and lapatinib carried out in advanced solid tumors, the optimal tolerated regimen was determined to be lapatinib 1,250 mg plus capecitabine 2,000 mg/m2/day. At these dose levels, the combination was well tolerated with few grade 3 toxicities and no grade 4 toxicity. Our preclinical work suggested synergistic activity of capecitabine and lapatinib in pancreatic cancer. We initiated a study of this combination in the first-line therapy of metastatic pancreas cancer. Methods: This was a single-arm multicenter study in patients with chemotherapy-naive metastatic pancreatic cancer. The primary endpoint was overall survival. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 12 patients. If at least seven of these patients survived for at least six months, then a further 20 patients would be enrolled into the study. If six or fewer of the initial 12 patients met the specified study survival criteria, the study would be halted. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Clinical and laboratory parameters were assessed to evaluate disease response and toxicity of therapy. The study patients received lapatinib 1,250 mg/day, plus capecitabine 2000 mg/m2/day on days 1-14 every 21 days. Results: Nine patients were enrolled. Seven of these patients did not achieve the interim protocol response requirement of survival for at least 6 months, to allow for the study to continue to the second cohort of patients. Median overall survival from first dose was 4 months. Median time on treatment was 2 months. There were no objective responses. There were no unexpected toxicities. Conclusions: The addition of lapatinib to capecitabine does not improve overall survival in the first-line treatment of advanced pancreatic cancer patients. [Table: see text]
Adjuvant chemoradiation for resected gallbladder cancer.
Authors: Muller B. G. , Sola J. A. , Carcamo M. , Sola A. , Ciudad A. M. , Trujillo C. 
Published: February 2017

319 Background: Gallbladder cancer (GBC) is the leading cause of cancer death in women in Chile. Even after curative surgery, prognosis is grim. To evaluate acute and late toxicity and efficacy in terms of overall survival of adjuvant chemoradiation (CR) after curative resection of GBC. Methods: We retrospectively analyzed the cohort of patients with curatively resected GBC diagnosed between January 1999 and April 2009, treated with adjuvant CR at the Instituto Nacional del Cáncer, Santiago de Chile. Treatment protocol considered external beam radiation therapy (RT) (45–54 Gy) to tumor bed and regional lymphnodes with concurrent 5-fluorouracil (5-FU) (500 mg/m2/day by 120-h continuous infusion on days 1-5 and 29-33). Data was obtained from medical records, mortality from death certificates. NCI CTC v 3.0 was used for toxicity grading, and 6th Edition of AJCC Cancer Staging Manual for staging. Survival was estimated by Kaplan- Meier curves. Results: 45 patients with curatively resected GBC received adjuvant CR. Mean age was 56 years (range 33-75), 38 patients were female. All patients had PS 0 or 1 at baseline. After diagnosis a second surgery was performed in 41 patients. Cholecystectomy with hepatic segmentectomy and lymphadenectomy was the curative surgery in 40 patients. For tumor and staging details see the Table. All patients received RT with a planned dose of 45 Gy in 25 fractions. 9 patients received a boost to the tumor bed up to 54 Gy. Three patients stopped RT early. 33 patients had concurrent 5-FU, 31 completed treatment as planned. Therapy was well tolerated, only 4 grade 3 toxicities were observed (1 neutropenia, 1 thrombocytopenia, 2 elevated alkaline phosphatase). No grade 4 or 5 toxicity was observed. No grade >2 late toxicity was observed. Twenty two patients have died. Median survival was 26 months, with 3- and 5-year overall survival of 64% and 46% respectively. Conclusions: Adjuvant chemoradiation with 5-FU is well tolerated and might impact favorably on survival in patients with curatively resected GBC. [Table: see text] No significant financial relationships to disclose.
A phase II multicenter trial of neoadjuvant chemotherapy FOLFOX6 in combination with bevacizumab for patients with resectable synchronous liver metastases after R0-resections of primary colorectal cancers: The interim analysis.
Authors: Miura K. , Katayose Y. , Oikawa M. , Yamauchi J. , Sakurai N. , Musha H. , Narushima Y. , Nakagawa K. , Egawa S. , Unno M. ,   Miyagi HBPCOG
Published: February 2017

322 Background: Therapeutic strategies for colorectal cancer (CRC) patients with synchronous liver metastases are still indeterminate; therefore, we conducted a phase II multicenter trial of neoadjuvant chemotherapy mFOLFOX6 combined with bevacizumab for resectable synchronous liver metastases after R0-resections of primary CRCs. This study was started in June 2008. This is the interim report. Purpose: The aim of this interim analysis is to evaluate the response rate (RR) and adverse events (AEs) of the enrolled patients. Methods: Eligibility criteria included CRC patients with 10 or less synchronous liver metastases that were preoperatively diagnosed as surgically resectable. 20 of the enrolled patients received 8 courses of mFOLFOX6 with bevacizumab, but bevacizumab was omitted at the initial and the final courses, to avoid the AEs at the operations. The primary endpoint was the RR. Results: Among the 20 patients, one patient was excluded from the study because the assumed metastasis was diagnosed to be hemangioma later with the MRI imaging. RR was analyzed for the 19 patients, and AEs were analyzed for the 20 patients. Complete response and partial response were achieved in 2 (10.5%) and 11 (57.9%), respectively (RR: 68.4%); 4 (21.1%) were stable disease, and 2 (10.5%) were progressive disease. The RR was higher than the prespecified boundary; therefore, this study was scheduled to be continued. AEs were the following: neutropenia, hypertension, anemia, leucopenia, nausea, appetite loss, stomatitis, bleeding and proteinuria. Grade 3 neutropenia occurred in 4 cases (20.0%), and sensory neuropathy, stomatitis, diarrhea, and cerebral infarctions occurred in each one (5.0%) of the patients. There was no AE of grade 4 or 5. Liver resections were performed in 17 cases, and R0-resection was achieved in all of the operable cases (R0 rate was 85%). Conclusions: Neoadjuvant chemotherapy mFOLFOX6 combined with bevacizumab appears to be effective and well tolerated. The study is continued as scheduled, to further evaluate the benefit of this regimen. No significant financial relationships to disclose.
Comparison of the efficacy of gemcitabine with capecitabine and gemcitabine with erlotinib combination chemotherapy in recurrent or advanced pancreatic cancer as first-line treatment: Single-center experience.
Authors: Chun S. , Lee M. , Jeon E. , An H. , Hong T. , You Y. , Kim D. , Lee I. 
Published: February 2017

329 Background: We compared the efficacy and toxicity of gemcitabine with capecitabine (GX), and gemcitabine with erlotinib (GT) chemotherapy for recurrent or advanced pancreatic cancer by retrospective analysis. Methods: Between October 2006 and June 2010, 44 patients with recurrent or advanced pancreatic cancer, diagnosed at Seoul St. Mary's hospital were enrolled. In GT group, gemcitabine 1000mg/m2 was administered on days 1, 8, 15, 22, 29, 36, 43 followed by a 1-week rest in first treatment cycle (8 weeks), and then D1, 8, 15 followed by a 1-week rest. Erlotinib was taken orally at 150mg daily through the entire cycle. In GX group, gemcitabine 1000mg/m2 was administered on days 1 and 8. Capecitabine was taken orally at 650mg/m2 twice daily on day 1-14 of a 21-day cycle. Results: In 44 patients, 26 patients were treated with GT, and 18 patients treated with GX. The median age was 56.58 years in GT and 57.67 years in GX. Median number of cycle was 3.04 in GT and 3.57 in GX, and the dose reduction was significantly more common in GX than GT (50% vs. 19%, p=0.031). No complete response was achieved in either group. In GT, partial response and stable disease were achieved in 6 (23.1%) and 8 (30.8%) patients. In GX, partial response and stable disease were shown in 4 (22.2%) and 7 (38.9%) patients, respectively. No significant differences in two patients groups (p=0.442). GX had more favorable clinical outcome of the time to progression (6.1 months vs. 3.0 months, p=0.002) and the overall survival (11.13 months vs. 6.1 months, p=0.012) than GT. The most common grade 3 or 4 toxicity in GT and GX treatment were hematologic toxicity: anemia (8.3%:0%), neutropenia (34.6%:38.8%), thrombocytopenia (15.4%:11.1%). Grade 3 or 4 hand-foot-syndrome of GX was reported in only one patient. Conclusions: GX showed better time to progression and overall survival outcome than GT, but dose reduction was more common. Although there was no significant difference in response rate, and the less dose intensity, GX regimen may be more effective than GT in advanced pancreatic cancer. Further prospective, randomized trials would be warranted in large scale. No significant financial relationships to disclose.
Prospective phase II study of chemoembolization with drug-eluting beads for hepatic neuroendocrine metastases: Interim analysis.
Authors: Reyes D. K. , Kamel I. R. , Georgiades C. , Hong K. , Bhagat N. , Geschwind J. H. 
Published: February 2017

331 Background: To evaluate safety and efficacy of transarterial chemoembolization with doxorubicin eluting beads (DEB-TACE) in 30 patients with hepatic neuroendocrine metastases (NET) in a prospective phase II study. We report the interim analysis on 10 patients. Methods: Patients who met inclusion criteria (NET liver-dominant metastases, ECOG 0-1, treatment naïve) underwent up to 4 DEB-TACE sessions (100-300 micron beads loaded with up to 100mg of doxorubicin) within a 6-month period. Statistical plan included interim analysis of initial 10 patients to assess therapeutic efficacy (defined as objective response≥50%). Tumor response was assessed by MR imaging 1 month after treatment using contrast-enhancement (EASL) and tumor size (RECIST). Safety was assessed by NCI Common Terminology Criteria. Results: DEB-TACE was successfully performed in 10 patients (22 targeted lesions). Patient characteristics included mean age 65 yrs; ECOG 0/1 (6/4); carcinoid syndrome (n=2); tumor burden range (4-75%), and mean targeted tumor size 4.8 cm (range 1.2-10.2). At one month follow-up (n=9), Grade 3 toxicities consisted of hyperglycemia (n=3), abdominal pain (n=3), fatigue (n=1), biloma (n=1) and elevated ALT (n=1). Note that four patients had Grade 2 bilomas, which occurred in the setting of small lesions (<2cm), diffuse disease with very low tumor burden (near military pattern), and single lesion ≥ 5cm. Tumor response using MR imaging at 1 month-follow-up revealed a mean treated tumor decrease in size of 7% (p=0.03), and a mean decrease in contrast-enhancement of 59% (p<0.0001). Using RECIST, partial response was achieved in 1 patient (11%), whereas 8 patients (89%) had stable disease. Using EASL criteria, 7 patients (78%) had objective tumor response and 2 (12%) had stable disease. Conclusions: Interim analysis shows therapeutic efficacy of DEB-TACE in liver-dominant NET metastases. Early recommendation suggests DEB-TACE may be best suited for NET patients with multifocal disease or diffuse disease with large tumor burden. [Table: see text] No significant financial relationships to disclose.
Stereotactic body radiation therapy in the treatment of unresectable intrahepatic cholangiocarcinoma.
Authors: O'Connor J. , Goldstein R. 
Published: February 2017

335 Background: Unresectable intrahepatic cholangiocarcinoma has a poor prognosis with less than 5% of patients surviving 5 years. We review our experience with stereotactic body radiation therapy (SBRT) in the treatment of unresectable intrahepatic cholangiocarcinoma and evaluate acute toxicity and local control. Methods: From November 2005 until August 2010, 12 patients with unresectable intrahepatic cholangiocarcinoma were treated with SBRT. All patients were evaluated by a liver surgeon and were deemed unresectable prior to radiosurgery. The median tumor size was 4.3 cm (range 1.9–9.3 cm). All tumors were located in the right hepatic lobe. Three patients had received prior radiation therapy and SBRT was given as a boost with a median dose of 24 Gy in three fractions. Nine patients received SBRT as the sole local modality to a median dose of 51 Gy (range 30–55 Gy) in three fractions on consecutive days. Local control was determined by follow-up imaging with MRI. The median follow up is 12 months. Toxicity was assessed using Common Toxicity Criteria (CTC) guidelines version 3.0. Results: Overall, only 3 of 12 (25%) patients experienced acute toxicity. Three patients had abdominal discomfort and one patient had nausea. All toxicities were grade 1. Ten of 12 (83%) patients received chemotherapy. Four patients received chemotherapy before SBRT and five patients received chemotherapy after. One patient received chemotherapy before and after SBRT. Overall local control is 75% for eight patients with follow-up imaging. Two of eight (25%) patients had a complete response. Four of eight (67%) patients had a partial response or stable disease. One patient had a local recurrence 13 months after receiving SBRT (51 Gy in three fractions) and was retreated with SBRT (28 Gy in three fractions) with no acute toxicity. There was no difference in outcome whether SBRT was given before or after chemotherapy. Conclusions: Stereotactic body radiation therapy given sequentially with chemotherapy is well tolerated with few side effects in the treatment of unresectable intrahepatic cholangiocarcinoma and early local control is promising. No significant financial relationships to disclose.
Use of the Optimata Virtual Patient (OVP) to predict effects of sunitinib malate in advanced pancreatic cancer.
Authors: Kleiman M. , Shacham S. , Kushnir M. , Chapnik E. , Agur Z. 
Published: February 2017

341 Background: Pancreatic cancer is considered to be incurable by available treatment modalities, with 5-year survival rate <4%. Sunitinib malate (Sutent) significantly increased progression-free survival in patients with advanced islet cell tumors (pancreatic); however, it demonstrated only modest single-agent effect in a phase II study in patients with metastatic pancreatic adenocarcinoma (PaC) that progressed after first-line therapy with gemcitabine. To improve the response of PaC patients to drugs, the interplay between biologic, pathologic, and pharmacologic processes underlying drug-patient interactions have been mathematically modeled, predicting efficacy responses, different toxicities, and long-term tolerability in clinical trials, allowing for improved dosing regimens and patient selection (OVP engine) (Agur Z., 2010). The OVP engine was used to predict Sunitinib malate single-agent activity in advanced PaC. Methods: OVP replicated the observed growth patterns of human PaC. Pharmacokinetics (PK) and pharmacodynamics (PD) of sunitinib malate were modeled based on literature (NDA 21-938). Effects of sunitinib malate on human PaC xenografts were scaled to model PK/PD in human. To evaluate drug efficacy in advanced PaC patient-population, a Virtual PaC Patient- Population was created by replacing the population averaged parameter values in the model by their distribution in the population. Using this procedure, a large set of virtual patients was generated. Model simulations with sunitinib malate therapy (50 mg QD/28 days; 14 days rest [1 cycle]) enabled the prediction and classification of patients' response according to RECIST criteria and compared with the actual clinical response (O'Reilly et al, 2008). Results: Simulations of the FDA-approved schedule, predicted a stable disease in 81% of the patients following one treatment cycle and 54% following two treatment cycles. Stable disease was predicted to be the best observed response, which was confirmed in the clinical study. Conclusions: Our model predictions are compatible with clinical results of a recent phase II trial with the same treatment regimen of sunitinib malate (O'Reilly et al, 2008) and further suggest the use of mathematical model during drug development. [Table: see text]
EXPERT-C: A randomized phase II European multicenter trial of neoadjuvant chemotherapy (capecitabine/oxaliplatin) and chemoradiation (CRT) with or without cetuximab followed by total mesorectal excision (TME) in patients with MRI-defined high-risk rectal cancer.
Authors: Dewdney A. , Cunningham D. , Tabernero J. , Glimelius B. , Cervantes A. , Tait D. M. , Brown G. , Wotherspoon A. , Gonzalez de Castro D. , Chau I. 
Published: February 2017

360 Background: We previously demonstrated the feasibility of administering neoadjuvant chemotherapy before CRT and TME in patients with MRI selected poor prognosis rectal cancer (Chua Y J et al Lancet Oncol 2010). This trial evaluates the addition of the anti-EGFR antibody cetuximab to this treatment strategy. KRAS and BRAF mutations have been established as predictive for lack of response to anti-EGFR therapy in metastatic colorectal cancer. Methods: Patients with newly diagnosed, histologically confirmed, MRI defined high risk rectal adenocarcinoma were randomised to receive 4 cycles of capecitabine 1,700mg/m2 with oxaliplatin 130mg/m2 (CAPOX) followed by CRT, 45Gy/25# + 5.4Gy/3# boost with concurrent continuous capecitabine 1,650mg/m2/day, TME and 4 cycles of adjuvant CAPOX (EXPERT) or the same regimen with the addition of cetuximab (400mg/m2 loading dose week 1, followed by 250mg/m2/week) (EXPERT-C). The primary endpoint is complete response (CR) (defined as pathological complete response or radiological complete response in patients who decline surgery) in KRAS and BRAF wild type tumours. Secondary endpoints include radiological response to CRT, CR in both KRAS wild type and mutant patients, R0 resection rates, progression free and overall survival and safety. Results: Between 2005-2008, 165 eligible patients were recruited from 15 centres (EXPERT n=81, EXPERT-C n=84). 99% of patients had performance status 0-1, 98% had ≥ T3 disease, 56% had an involved or threatened circumferential resection margin and 72% had evidence of extramural venous invasion determined by MRI. The current median follow up is 30 months. 72/81 (89%) and 79/84 (94%) of patients completed neoadjuvant CRT and 72/81 (89%) and 77/84 (92%) patients underwent curative-intent surgery on the EXPERT and EXPERT-C arms respectively. Two patients declined surgery. Conclusions: The primary and secondary endpoints will be analyzed in October 2010 and will be presented at the meeting. [Table: see text]