bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase II study of gemcitabine plus zoledronic acid in subjects with Stage IV pancreatic cancer
Authors: Cox J. V. , Cartwright T. H. , Neubauer M. , McCollum D. , Sandbach J. , Monticelli M. A. , Boehm K. A. , Ilegbodu D. , Asmar L. 
Published: March 2020

14002 Background: Gemcitabine, the standard chemotherapy for advanced pancreatic cancer (APC), produces low response rates and short time to progression. Preclinical studies suggest that zoledronic acid inhibits pancreatic cell lines by interfering with the p21ras/raf-1/MEK1/ERKL signaling pathway. We conducted this trial to evaluate the efficacy and toxicity of gemcitabine and zoledronic acid in subjects with APC. Methods: Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma (Stage IV) not amenable to resection with curative intent. Gemcitabine 1000 mg/m2 IV was given on Days 1, 8, 15, and 22 in Cycle 1 and Days 1, 8, and 15 in subsequent cycles. Zoledronic acid 4 mg IV was given on Day 1 every 4 weeks. Toxicity was assessed at each visit. Results: Between December 2004 and July 2005, 35 subjects were enrolled. Baseline characteristics: 20 males (57%), median age 66.7 years (range, 40–83.5), and KPS of 70/80/90/100 = 8%/29%/34%/29%, respectively. Four patients had locally advanced disease (3 stage IIB and 1 stage III), 86% of subjects had Stage IV disease at diagnosis; 91% of subjects had adenocarcinoma. Prior therapy included surgery (n=15, 43%), chemotherapy (n=3, 9%), and radiotherapy (n=2, 6%). To date, there has been 1 PR and 9 SD; the clinical benefit rate (PR+SD≥6 months) was 14%. Grade 3 and 4 treatment-related toxicities included: neutropenia (22%); thrombocytopenia and fatigue, (12.5% each); and anemia, nausea/vomiting, dehydration, and diarrhea (6% each). Seven treatment-related SAEs have been reported; 28 subjects are off study. Patients discontinued treatment due to: progressive disease (PD) (n=15), toxicity (n=4, 1 each DVT, infection, back pain, and generalized weakness), withdrew consent (n=3), MD decision (n=2), patient request (n=2), and death (n=2), To date, 21 subjects have died; deaths were attributed to PD (n=16), CVA (n=1), and unknown (n=4). Conclusions: Pancreatic cancer, typically advanced at diagnosis, remains a major treatment challenge. Zoledronic acid in combination with gemcitabine was well-tolerated in this study. Future genomic testing is proposed for responders. Updated toxicity, response, and survival data will be presented. Supported by Novartis Pharmaceuticals Corp., East Hanover, NJ. No significant financial relationships to disclose.
Dose-finding study using oxaliplatin (Ox) in combination with fixed dose gemcitabine (Gem) and radiotherapy (RT) in patients with locally advanced pancreatic or biliary tract cancer (PBCa)
Authors: Peeters M. , Boterberg T. , Monsaert E. , Borbath I. , Demols A. , Polus M. , Scalliet P. , Berrevoet F. , Derre T. , Van Laethem J. 
Published: March 2020

14028 Background: Prognosis of inoperable PBCa is poor. Large randomized studies in pancreatic cancer showed a better survival in patients (pts) with locally advanced (LA) in comparison with metastatic disease. Data on radiochemotherapy are scarce in pts with LA disease. Therefore, we performed this multicenter, phase I study on the combination of radiotherapy and Gem/Ox. This regimen showed superior activity to Gem alone in pancreatic cancer (Louvet C et al. JCO 2005;23:3509–16.) Methods: After signed informed consent, pts with LA pancreatic cancer (n = 14) or biliary tract cancer (n=1) were included. They received two cycles of Gem/Ox1 followed by 5 weeks of RT (25 fractions of 1.8 Gy up to a total dose of 45 Gy) in combination with a weekly fixed dose of Gem (300 mg/m2 in 30’) and an escalating weekly dose of Ox (levels: 40/50/60 mg/m2). NCI-CTC 2.0 was used weekly to score treatment-related toxicity in all pts. Results: Today, 15 pts. with a median age of 61 y (range: 44–74), median Karnofsky performance score 90 (range: 70–100) and M/F = 8/7 were included. Upto 60 mg/m2 Ox, no disease limiting toxicity (DLT) occured. Grade 3 toxicity included nausea (n = 1), neutropenia (n = 3) and thrombocytopenia (n = 1). This latter patient was treated with 40 mg/m2 Ox and subsequently also experienced a grade 4. One patient receiving 50 mg/m2 Ox developed a grade 4 thrombocytopenia. Most frequent grade 1/2 toxicity was nausea (n = 8, 53%), thrombocytopenia (n = 5, 33%) and diarrhea (n = 5, 30%). Fourteen out of 15 received the full course of radiotherapy. Median time to progression (TTP) is 6.7 months (95% CI: 3.7–13.5). Thirteen out of 15 pts. are still alive. Conclusions: Combination of radiotherapy and Gemcitabin/Oxaliplatin in pts with LA pancreaticobiliairy cancer is feasible and well-tolerated. The long TTP underlines the potential activity of this regimen. As no DLT has been reached, we will use a dose of 60 mg/m2 Ox for further evaluation. [Table: see text]
Preliminary results of phase II study of irinotecan and capecitabine combination as first line chemotherapy for advanced and metastatic gastric cancer
Authors: Farhat F. , Bachour M. , El Seoudi M. , Kattan J. , Ghosn M. , Nasr F. , Moukadem W. , Younes F. , Mroueh R. , Chahine G. 
Published: March 2020

14030 Background: Chemotherapy has a proven palliative role in advanced gastric cancer. The most widely investigated single-agent chemotherapy is 5-fluorouracil with partial response rates up to 20%. Single-agent irinotecan achieved response rates of 18%-23%. We investigated the combination Irinotecan plus Capecitabine for previously untreated locally advanced or metastatic gastric cancer. Methods: We conducted a phase II study with the combination of Irinotecan 80 mg/m2 on day 1, 8, and 15, and capecitabine 625 mg/m2 twice daily on days 1 to 14 repeated every 4 weeks. Patients were evaluated every second cycle. Previous chemotherapy for metastatic disease was not allowed. Patients must have measurable disease, ECOG PS < 2, life expectancy > 2 months, adequate hematological, liver and renal functions. Response was evaluated according to RECIST and toxicities according to NCI common toxicity criteria 3.0. Results: Between February 2002 and December 2005 31 patients were enrolled (20 male and 11 female). The median age was 57 years [range 37–74 years]. 142 cycles were administered with a median of 4.6 cycles per patient [range 1–10 cycles]. 29 patients were evaluable for response, and two are on ongoing treatment. Partial response rate was 38.5% . 9 patients (29%) had stable disease. Overall tumor control rate was 67.5%. Median time to progression and overall survival were 5.8 months [range- 1–16] and 10.58 months [range- 1–21] respectively. There was no grade III-IV reported toxicity including no hand and foot syndrome. Conclusions: Irinotecan and capecitabine in combination show an interesting tumor control rate (67.5%) with extremely well tolerated toxicity in patients with extensive gastric cancer. No significant financial relationships to disclose.
Multicenter phase II study of pemetrexed and oxaliplatin as first-line therapy in advanced gastric cancer
Authors: Celio L. , Sachetta S. , Mosconi S. , La Torre I. , Barone C. , Berardi R. , Amoroso V. , Pinotti G. , Di Costanzo F. , Bajetta E. 
Published: March 2020

14045 Background: We have previously reported that single-agent pemetrexed is active in metastatic gastric cancer. On the basis of the potential synergism of pemetrexed and oxaliplatin, we explored the combination in patients with locally advanced/metastatic gastric carcinoma. Methods: The primary objective was activity of the combination. Eligible patients had to ≥1 measurable lesion according to RECIST. Pemetrexed 500 mg/m2 was given intravenously over 10 minutes, and oxaliplatin 120 mg/m2 was given over 2 hours; both drugs were given on day 1 of a 21-day cycle. Patients were to receive ≥6 (maximum of 8) cycles unless disease progression occurred. Vitamin supplementation was given as well as dexamethasone. A total of 43 patients were planned in a two-stage design with 13 patients in the first stage. An interim analysis was planned at the end of the first stage, so the trial could be stopped if ≤3 responses were observed. Results: Between May 2004 and January 2005, 13 patients (6 females) entered the study. Median age was 52 years (range, 27–75). One patient (7.8%) had locally advanced disease, and 5 patients (38.5%) retained primary gastric cancer. Main disease sites included lymph nodes (100%) and liver (23.1%). A total of 60 cycles were administered (median 6; range, 2–6). All 13 patients were evaluable for efficacy with 3 complete and 2 partial responses (ORR 38.5%; 95% CI, 13.9%-68.4%). Stable disease occurred in 3 patients (23.1%). G3 toxicities were neutropenia (30.8%), vomiting, hepatic toxicities and leucopenia (7.7%) each; no G4 toxicity were found. Conclusions: This interim analysis suggests that the activity and tolerability of the combination in advanced gastric cancer is very promising. Study accrual was ended in October 2005, and final results will be presented at the meeting. No significant financial relationships to disclose.
Phase II study of cisplatin, epirubicin, oral UFT, and leucovorin as first-line chemotherapy for metastatic gastric cancer
Authors: Idelevich E. , Karminsky N. , Dinerman M. , Katsenelson R. , Ben Zvi N. , Ben Baruch N. , Man S. , Shani A. 
Published: March 2020

14049 Background: A phase II study was conducted to assess the efficacy and tolerability of combination therapy with cisplatin, epirubicin, oral UFT and leucovorin in patients (Pts) with metastatic gastric cancer. Methods: Pts with previously untreated metastatic or unresectable measurable gastric adenocarcinoma received cisplatin 60 mg/m2 and epirubicin 50 mg/m2 on day (d)1, UFT 300 mg/m2 was administered in conjunction with oral leucovorin 30 mg/day in divided daily doses d 1–22, followed by a 7-day rest period. Results: Thirty-nine pts were enrolled in this study. Two achieved a complete response and 13 a partial response, giving an overall response rate of 38.5%. Disease stabilization was achieved in further 16 pts (41%). Median time to progression and median survival were 6.4 and 10.7 months respectively. Grade 3/4 neutropenia, anemia, throbocytopenia, occurred in 10%, 5%, and 2% of pts respectively, and febrile neutropenia occurred in 7 pts (one episode each). Grade 3 diarrhea occurred in 5% of the pts. There were no treatment related deaths. Conclusions: Cisplatin, epirubicin, and oral UFT plus leucovorin, a convenient outpatient regimen, has significant activity and tolerable toxicities in pts with metastatic gastric carcinoma. No significant financial relationships to disclose.
Adjuvant chemoradiotherapy for gastric adenocarcinoma: Kaiser institutional experience with INT 0116
Authors: Kerwin T. L. , Miller M. J. , Tome M. A. 
Published: March 2020

14114 Background: The standard of care for resectable gastric or gastroesophageal adenocarcinoma is total or partial gastrectomy followed by adjuvant chemoradiotherapy as defined by the Intergroup 0116 study. We have reviewed our institutional experience with this regimen in hopes of defining patient subsets which are most likely to benefit, as well as those who are least likely to benefit, such that alternative therapies may be recommended. Methods: A retrospective review was conducted for 38 consecutive patients treated for gastric or gastroesophageal adenocarcinoma with total or partial gastrectomy followed by chemoradiotherapy. Chemotherapy was with 5-FU 425 mg/m2/day and Leukovorin 20 mg/m2. Radiotherapy was with 45 Gy in 25 fx delivered through AP-PA fields or a 3-field technique, at the discretion of the treating physician. Results: The median patient age is 55 years old. The median follow-up is 29 months. There were 14 D0 resections, 21 D1 resections, and 3 D2 resections. The number of patients with N0, N1, N2, and N3 disease are respectively 4, 20, 11, 3. One patient did not complete treatment due to disease progression. There were positive margins in 8 patients. Four patients developed fatal treatment-related complications. Median overall survival for patients with positive margins is 19 months and for negative margins is 34 months. Median overall survival for N0/N1 patients is 36 months and for N2/N3 patients is 22 months. Eighteen patients recurred at a median of 14 months - 5 locally, 9 regionally in the abdomen, and 4 distantly. Death occurred in 16/18 recurrences. Conclusions: The overall survival of patients in this study is consistent with previously-reported data. The adequacy of surgical resection is relevant as it affects nodal staging. Positive margin status and advanced nodal involvement are predictors for poor outcomes, indicating that alternative therapies may be more appropriate for these patients given the potential toxicity of the current recommended treatments. No significant financial relationships to disclose.
Automatic segmentation of pancreatic images using ISODATA alorithm
Authors: Biswal B. , Shah N. , Shah N. , Trivedi M. , Nayak S. , Dave H. 
Published: March 2020

14149 Background: Pancreatic cancer is the second most common gastrointestinal malignancy in the United States, where it ranks 4th among all deaths caused by cancers. Early detection of pancreatic cancer remains a challange. Methods: MR images with different T1 and T2 weighting from the anatomical regions with the same imaging parameters were obtained. ISODATA segmentation algorithm, a multivariate method was used to reliable detect the various clusters in the data sets. Results: In all the four subjects, the pancreatic region was found to be from a different (and unique) cluster. This cluster covered the pancreatic region in all the four subjects. Conclusions: The ISODATA algorithm presented could detect the pancreatic region without manual tracing. No significant financial relationships to disclose.
Gemcitabine-based transcatheter arterial chemoembolization for unresectable cholangiocarcinoma in thirty-eight patients: Single institutional experience
Authors: Gamblin T. C. , Geller D. A. , Marsh J. W. , Carr B. 
Published: March 2020

14152 Background: Survival for patients with unresectable cholangiocarcinoma is reported to be 5–8 months. Systemic chemotherapy has been disappointing and not shown to significantly improve survival. Transcatheter arterial chemoembolization (TACE) has been shown to prolong survival in hepatocellular carcinoma patients but experience with cholangiocarcinoma is limited. We report our experience with the well-tolerated drug gemcitabine. Methods: Thirty-eight patients with unresectable cholangiocarcinoma were treated with one or more cycles of gemcitabine-based TACE between 2001 and 2005 at our institution. Follow-up imaging was performed on all patients after each TACE procedure. Regimens of TACE included: gemcitabine only (16), gemcitabine followed by cisplatin (2), gemcitabine followed by oxaliplatin (5), gemcitabine and cisplatin (12), and gemcitabine and cisplatin followed by oxaliplatin (3). Actual survival is reported, as 35 of 38 have died from disease (92%). Results: Patients were 57.5 years of age (range 36–87) and a median of 3 treatments (range 1–10) were administered. Median survival from time of first treatment was 10.3 months. Patients receiving gemcitabine followed by cisplatin or oxaliplatin had improved survival (mean 16.5 and 10.5 months respectively) when compared to gemcitabine alone (mean 6 months). Patients receiving gemcitabine and cisplatin as a combination had improved survival (mean 13.4 months) compared to single agent gemcitabine. Patients who progressed on gemcitabine and cisplatin and then received oxaliplatin also showed improved survival (mean 14.3 months) compared to gemcitabine only. Neutropenia, thrombocytopenia and hyperbilirubinemia were the most common toxicities observed. Three patients in the entire series exhibited grade 3 thrombocytopenia while seven patients had grade 3 and one had grade 4 bilirubin levels. Conclusions: This series provides evidence in favor of TACE rather than historically reported alternatives such as systemic chemotherapy or chemotherapy/RT. Our results suggest that gemcitabine based TACE is well tolerated and perhaps best delivered as a combination therapy for patients with unresectable cholangiocarcinoma. No significant financial relationships to disclose.
Magnetic resonance imaging of the bone marrow (MRBM) as an outcome measure for patients with metastatic prostate cancer
Authors: Gignac G. A. , Morris M. J. , Schwartz L. H. , Lis E. , Scher H. I. 
Published: March 2020

14521 Background: Previously we have shown that the distribution of osseous metastases in prostate cancer (PC) matched the distribution of the normal adult marrow. Over 90% of advanced PC patients have disease in bone. Imaging the marrow has the potential to allow detection of metastases before osseous response has occurred and provides a three dimensional volumetric measure that can be quantified and monitored serially for changes over time. We are examining the use of MRBM as an indicator of treatment effect in patients with metastatic PC. Methods: Patients with PC and 2 or more MRBM surveys were identified and extracted from a database of all patients at MSK who have had radiologic studies. Cases were further identified on the basis of having metastatic disease, followup MRBM within 4–7 months, concurrent PSA and bone scans. MRI reports were stratified as either “progression” or “stable/improved” assuming a clinician would change therapy if progression was documented. PSA was similarly recorded, using a definition of ≥ 25% increase from baseline to indicate progression. Bone scans were stratified on the basis of new lesions verses no new lesions. Results: Twenty-five patients were eligible for review with a median baseline PSA of 7.34 ng/ml (0.05–473 ng/ml). Average percent change of PSA at followup was 651% (0–11033%). Treatment included: hormones (11), chemotherapy (5), calcitriol (4) and observation (5). The change in MRBM was concordant in 73% of patients with progression by PSA. These results are demonstrated below in the Table. Conclusions: MRBM is a novel means to assess metastatic disease to bone. This preliminary analysis suggests that MRBM can be early indicator of treatment failure. We plan to explore it prospectively as an outcome measure for PC using a lesional analysis. Grant Support: PEPSICO, PCF, NCI 102544, CA102544 and 5T32CA09207. [Table: see text] [Table: see text]
Long-term survival following nephrectomy for renal cell carcinoma: The 15 year University of California-Los Angeles experience
Authors: Lam J. S. , Goel R. H. , Pantuck A. J. , Figlin R. A. , Belldegrun A. S. 
Published: March 2020

14532 Background: Significant advances in the diagnosis, staging, and treatment of patients with renal cell carcinoma (RCC) during the last 2 decades have resulted in improved survival of a select group of patients and an overall change in the natural history of the disease. We describe the pathologic characteristics and long-term survival in patients treated for localized and metastatic RCC at a single tertiary care institution. Methods: Between 1990 and 2005, 1431 patients diagnosed with a renal mass underwent surgical resection and were evaluated for differences in clinicopathologic characteristics and survival based on the University of California-Los Angeles Integrated Staging System (UISS). Data were analyzed using standard statistical methods. Results: Following surgical resection, RCC was found in 1269 patients at pathologic evaluation. Of these patients, 473 had evidence of metastatic dissemination at time of surgery. The primary tumor in patients with metastatic disease was more likely to be clear cell (78.8% vs. 72.9%, p = 0.02), collecting duct (1.3% vs. 0.1%, p = 0.01), or undifferentiated (4.8% vs. 1.6%, p = 0.002) RCC, and less likely to be papillary (12.0% vs. 18.7%, p = 0.002) or chromophobe (3.1% vs. 6.7%, p = 0.006) RCC compared to patients with non-metastatic disease, respectively. The 2-year, 5-year, and 10-year survival was significantly higher in non-metastatic patients compared to patients with metastatic disease present at time of surgery (87.0% vs. 42.4%, 70.0 vs. 21.8%, 50.0% vs. 16.5%, p < 0.001, respectively). Conclusions: Over the last 15 years, patients with non-metastatic disease at the time of surgery have improved survival rates and are more likely to have papillary or chromophobe primary tumors than patients with metastatic disease. UISS stratification of patients with RCC provides a unique tool for risk assignment and outcome analysis to help determine follow-up regimens and eligibility for clinical trials. [Table: see text] No significant financial relationships to disclose.
Biomarkers and obesity in surgically treated patients with prostate cancer
Authors: Shazer R. , Bharne A. , Nepomuceno E. , Mirocha J. , Ramirez C. , Luthringer D. , Holden S. , Agus D. B. , Gross M. 
Published: March 2020

14536 Background: Obesity is associated with poor outcomes in prostate cancer (PC). We explored if biomarkers for proliferation and estrogen signaling relate to obesity and surgical outcomes in PC patients (pts) treated by radical prostatectomy (RP). Methods: Pts with RP at a single institution between 1993 and 2002 were reviewed (1156 pts). The analysis subset included pts with full preoperative staging and anthropometric variables (541 pts). Clinical variables examined included: age, PSA, pre-operative hemoglobin (Hgb), ethnicity, and body mass index (BMI). Surgical outcomes included: estimated blood loss (EBL), Gleason score ≥ 7 (GS >7), extra-capsular extension (ECE), positive margins (MR+), and pathologic stage (pT2 vs. pT3/T4). Biomarkers examined in a convenience subset (n = 61) included proliferation index (Ki67% in cancer cells) and ERα positivity (nuclei staining ≥5% in cancer or peri-tumoral stromal cells). Obesity was defined as BMI ≥ 30 kg/m2. A step-wise logistic regression analysis was used to determine odds ratio (OR) in relation to obesity. Results: Mean ± standard deviation for pre-operative data included: age 62.7 ± 7.5 yrs; PSA 8.4 ± 6.8 ng/dl; Hgb 13.6 ± 1.8 g/dl; and BMI 26.5 ± 3.8 kg/m2. Pt reported ethnicities included: white (432 pts), Black/African-American (69 pts), Asian/Pacific Islander (20 pts), Hispanic (16 pts). BMI correlated highly with race (Kruskal-Wallis p = 0.002) and weakly with EBL (Spearman 0.11, p = 0.009) and Hgb (Spearman 0.15, p = 0.002). No correlation was observed between obesity and Gleason score. Regression models showed obesity was independently associated with ECE (OR 2.5, 95% CI 1.2–5.3) and pT3/T4 (OR 1.9, 95% CI 1.0–3.3). Biomarker analysis showed Ki67% correlated with GS >7, (Spearman 0.25, p = 0.048), but not BMI. No ERα positivity was noted in cancer cells. Stromal ERα positivity was noted in 21/30=70% of non-obese and 15/31=48% of obese pts (Fisher’s exact test p = 0.12). Conclusion: We confirm the association between obesity, ethnicity, and poor surgical outcomes. Biomarker analysis shows that obesity has no effect on proliferation index or tumor grade. However, we observe a trend towards down-regulation of stromal ERα expression in obese patients. No significant financial relationships to disclose.