bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I trial of biweekly S-1, leucovorin, oxaliplatin, and gemcitabine (the SLOG regimen) in metastatic pancreatic adenocarcinoma (mPDAC).
Authors: Chiang Nai-Jung , Tsai Kelvin K. , Chen Jen-Shi , Yang Shih-Hung , Hsu Chiun , Shan Yan-Shen , Chen Li-Tzong 
Published: February 2017

369 Background: Gemcitabine and S-1 had been approved as the frontline treatment for mPDAC in Taiwan and Japan. Our previous study showed biweekly gemcitabine plus modified FOLFOX4 (the GOFL regimen) was a moderate active and well-tolerated regimen in mPDAC. To explore whether oral S-1/LV can be a substitute for infusion 5-FU/LV in combination with gemcitabine and oxaliplatin as “the SLOG regimen” to improve treatment efficacy and convenience. To define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and preliminary anti-tumor efficacy of SLOG in patients with chemo-naïve mPDAC. Methods: Enrolled patients would receive intravenous infusion of 800 mg/m2 gemcitabine (fixed-dose rate infusion, 10 mg/m2/min) followed by 85mg/m2 oxaliplatin (2 hours) on D1 and escalating dose of oral S-1 and 20 mg/m2 leucovorin, twice daily D1-D7, every 14 days. DLTs were evaluated during the first 2 cycles of treatment. The treatment was continued until disease progression, unacceptable toxicity or withdrawal of informed consent. Results: 19 patients were enrolled into four dose levels of S-1, 20 mg/m2 (three), 30 mg/m2 (seven), 35 mg/m2 (six) and 40 mg/m2 (three). At 30 mg/m2 dose level, one patient who withdrew consent after one cycle treatment was replaced with another one. DLTs were observed in three patients, one at 30 mg/m2 (grade 3 diarrhea) and two at 40 mg/m2 (grade 3 hypersensitivity reaction and diarrhea in one each). MTD of S-1 was determined as 35 mg/m2. The median treatment duration was 8 cycles (ranged, 1-26). Of the 16 evaluable patients, the objective response rate and disease control rate were 37.5% (6 partial response, PR) and 81.3% (6 PR + 7 stable disease, SD), respectively. The median progression-free survival (PFS) was 4.6 months. At MTD dose level, there were 4 PR and 2 SD, with 6.7 months of PFS. The most common grade 3-4 adverse events included neutropenia (26.4%), diarrhea (15.8%), ALT increased (10.5%) and anemia (10.5%). Conclusions: The MTD of S-1 was 35 mg/m2 in the SLOG regimen. Extension phase II study in mPDAC is ongoing. Clinical trial information: NCT 01415713.
A multi-institutional phase II study of high-dose hypofractionated proton beam therapy (HF-PBT) for unresectable primary liver cancers: Long-term outcomes in patients (pts) with hepatocellular carcinoma (HCC).
Authors: Hong Theodore S. , Wo Jennifer Yon-Li , Ben-Josef Edgar , McDonnell Erin , Drapek Lorraine C. , Blaszkowsky Lawrence Scott , Kwak Eunice Lee , Clark Jeffrey W. , Goyal Lipika , Ryan David P. , Javle Milind M. , Arellano Ronald , Wolfgang John A. , Mullen John Thomas , Ferrone Cristina , Tanabe Kenneth , DeLaney Thomas F. , Crane Christopher H. , Zhu Andrew X. 
Published: February 2017

376 Background: Retrospective reports of PBT in hepatocellular carcinoma (HCC) demonstrate local control (LC) rates exceeding 85%. We prospectively replicate these findings and explore predictors of overall survival (OS) in pts with unresectable HCC receiving high dose, HF-PBT. Methods: Pts were enrolled on an NCI sponsored, multi-institutional, phase II study (NCT00976898). Key eligibility were unresectable HCC; Child’s A/B; ECOG PS 0-2; no extrahepatic disease; no prior RT. Maximum tumor size was 12 cm if solitary, 10 cm if 2 tumors, and 6 cm if 3. PBT was given in 15 fractions to a maximum total dose of 67.5 GyE. Sample size was calculated to demonstrate > 80% LC at 2 yrs (LC-2). Results: From 2009-2015, 44 patients were treated. Median age was 70 years (53-89) and 37 (84.1%) were male. 35 (79.5%) pts had Child A or no cirrhosis. 32 (72.7%) pts had 1 tumor, 12 (27.2%) had multiple tumors. Median longest tumor dimension was 5.0 cm (range 1.9-12.0). Median baseline AFP was 18.6 ng/mL (range 1.3-66081) and 29 pts (67.4%) had elevated AFP ( > 7.9 ng/mL). Median RT dose delivered was 58.0 GyE (range 40.5-67.5). 1 pt (2%) had grade 3 RT related toxicity (thrombocytopenia). With a median follow up 21.8 mo among 28 survivors, the LC-2 was 94.8% (95% CI 84.5-99.1%). mOS was 49.9 mo (95% CI 17.8 months- upper limit not reached) and mPFS was 13.9 mo (95% CI 8.4-49.9). OS did not differ by CLIP score, PS, prior treatment, vascular thrombus, baseline AFP, size, or dose. Median AFP change from baseline to 3 mo post treatment was a 32.8% reduction. Median time to AFP nadir in pts with elevated baseline levels was 3.9 mo (0-30.5). % decrease in AFP from baseline to 6 mo post-treatment was significantly associated with lower hazard of death. (HR = 0.993, p = 0.016). Conclusions: High dose hypofractionated proton beam therapy demonstrated a high local control rate for HCC with favorable safety profiles, supporting the ongoing evaluation of radiation in HCC in phase III studies. AFP decrease from baseline to 6 months post-radiation is associated with improved overall survival. Clinical trial information: NCT00976898.
Multidisciplinary management of pancreatic adenocarcinoma with isolated pulmonary metastases.
Authors: Jain Supriya K. , Meguid Cheryl , Leong Stephen , Edil Barish H. , McCarter Martin , Schefter Tracey E. , Schulick Richard D. , Lieu Christopher Hanyoung 
Published: February 2017

384 Background: Metastatic pancreatic adenocarcinoma (PAC) with isolated pulmonary metastases has recently been associated with prolonged overall survival. The purpose of this study was to review multi-disciplinary management and outcomes of these patients. Methods: Patients with PAC with pulmonary-only metastases were queried between 2012 to 2015 from a prospective single-institutional database. Results: Ten patients (median age: 71 yrs) were identified. Median number of lung metastases at diagnosis was 3 (range: 1 to innumerable). Seven patients had biopsy-proven lung metastases. Five presented with synchronous metastatic disease and five developed metachronous lung metastases as their first site of progression. Median time to progression between diagnosis of primary cancer to diagnosis of pulmonary metastases was 15 months (range: 4 to 31). Seven patients are alive as of this analysis. Median overall survival (OS) of this series (including two patients diagnosed 3 and 6 months ago) is 17 months, with longest overall survival = 40+ months (patient is still alive). All patients received gemcitabine-based chemotherapy; however, systemic regimens differed and included investigational agents. 3 of 5 patients with metachronous metastases underwent pancreaticoduodenectomy and are long-term survivors (34-40+ months). 2 of these 3 patients had diagnostic VATS of lung metastases and are alive with overall survival of 36+ months (resection of 2/3 nodules) and 34+ months (resection of all visible disease). Two patients with metachronous disease underwent neoadjuvant chemotherapy and pancreatic SBRT with progression to lung prior to planned surgery (OS: 30 months (deceased) and 6+ months (recently diagnosed)). 0 of 5 patients with synchronous metastatic disease had surgical resection; 3 of 5 received pancreatic SBRT. 3 of 10 patients are deceased due to visceral disease (14 months), pulmonary failure (18 months), and unknown causes (30 months). Conclusions: We report a recent single-institutional series of PAC with isolated lung metastases. Our data support that metastatic PAC patients with isolated pulmonary metastases have prolonged overall survival and suggest that local intervention may be beneficial.
Impact of chemotherapy and external beam radiation therapy on outcomes among patients with resected gallbladder cancer: A multi-institutional analysis.
Authors: Kim Yuhree , Amini Neda , Wilson Ana , Ethun Cecilia Grace , Poultsides George A. , Tran Thuy , Idrees Kamran , Isom Chelsea A , Fields Ryan C. , Weber Sharon M. , Salem Ahmed I. , Martin Robert C. G. , Scoggins Charles Raben , Shen Perry , Mogal Harveshp , Schmidt Carl Richard , Hatzaras Ioannis , Shenoy Rivfka , Maithel Shishir Kumar , Pawlik Timothy M. 
Published: February 2017

387 Background: Use of adjuvant chemotherapy (CTx) and chemoradiation therapy (cXRT) in the treatment of resectable gallbladder cancer remains varied. We sought to define the utilization and effect of adjuvant therapy on patients having undergone curative-intent resection for gallbladder cancer. Methods: Using a multi-institutional national database, 291 patients with gallbladder cancer who underwent curative-intent resection between 2000 and 2015. Patients with metastasis or an R2 margin were excluded. The impact of adjuvant therapy on survival was analyzed among patients who received surgery alone versus CTx versus cXRT. Results: Median patient age was 66 years. Most patients had a T2 (41.9%) or T3 (35.1%) lesion and 37.8% of patients had lymph node (LN) metastasis. A total of 186 (63.9%) patients underwent surgery alone, 61 (21.0%) received CTx, whereas the remaining 44 (15.1%) patients received cXRT. At a median follow-up of 16.3 months, median and 5-year overall survival (OS) was 28.3 months and 33.0%, respectively. On multivariable analysis, factors associated with worse OS included AJCC T3/T4 (hazard ratio [HR] 2.97), LN metastasis (HR 1.75) and lymphovascular invasion (HR 1.98; all P<0.05). In contrast, receipt of CTx or cXRT was associated with improved long-term OS (CTx, HR 0.33; cXRT, HR 0.27; P<0.001) compared with surgery alone. Similar results were observed for disease-free survival (DFS)(CTx, HR 0.53; cXRT, HR 0.45; P<0.01). Of note, the OS benefit for CTx or cXRT was observed among patients with high risk features such as AJCC T3/T4 disease (HR 0.61; HR 0.31), LN-metastasis (HR 0.45; HR 0.46), and R1 disease (HR 0.33; HR 0.11) (all P<0.05). In contrast, the OS benefit of CTx and cXRT was not noted among patients with T1/T2 or N0 disease, or among those with an R0 margin (all P>0.05). Conclusions: Adjuvant CTx and cXRT were utilized in 36% of patients undergoing curative-intent resection for gallbladder cancer. After adjusted analysis, CTx and cXRT were independent factors associated with improved long-term outcomes, but the benefit was isolated to only patients with high-risk characteristics.
Treatment strategy for intrahepatic cholangiocarcinoma: From optimal surgical management to adjuvant therapy.
Authors: Morine Yuji , Shimada Mitsuo , Imura Satoru , Ikemoto Tetsuya , Saito Yu , Yamada Shinichiro , Yoshikawa Masato , Teraoku Hiroki 
Published: February 2017

392 Background: Surgical strategy for intrahepatic cholangiocarcinoma (IHCC) including systemic lymph nodes (LN) dissection is still controversial. Also, as adjuvant chemotherapy, we adopted this GFP regimen (GEM, 5-FU, and Cisplatin). We demonstrate the adequate surgical strategy, the effect of adjuvant therapy and the tumor malignancy evaluation. Methods: Study 1: Surgical strategy) In period 1 (1994.4-2004.3, n = 20), extended surgery was basically performed. In period 2 (2004.4~, n = 34), extent of hepatectomy is conducted according to tumor conditions. Swelling LN exterpation for macroscopic curability and bile duct resection for positive surgical margin are performed. Study2: Adjuvant GFP therapy) Induction of 2 cycles of GFP for advanced IHCC with prognostic factors (LN metastasis, intrahepatic metastasis and R2 resection). Study 3: Malignancy evaluation) Significance of serum CA19-9 levels, the relationships its levels and expressions ( immunostaining ) of hypoxic inducible factor 1 (HIF-1) /Histone deacetylase 1 (HDAC1) were evaluated. Results: Study 1) In period 2, LN dissection and extrahepatic bile duct resection were significantly infrequent. Surgical outcome is rather good regardless of limited surgery in recent periods (Period 1 vs. Period 2: 5yrs survival 24.9% vs. 34.9%, p = 0.119). There was no significant difference in recurrent pattern. Study 2) There were 32 cases had some kind of prognostic factors, and of these 11 patients received adjuvant GFP. Patient’s prognosis received adjuvant GFP was significantly prolonged (GFP vs. non GFP: 1yrs survival 71.6% vs. 45.0%, p < 0.02). Study 3) CA19-9 ( > 300U/ml) high group revealed the independent prognostic factor with stepwise model, as well as LN metastasis and vessels invasion. CA19-9 levels significantly correlated to HDAC1 and HIF-1 expressions. Conclusions: Extended surgery including LN dissection might not control malignant behavior of IHCC, and adjuvant GFP should be introduced in patients with poor prognostic factors.
Intention to treat analysis of neoadjuvant chemoradiation and liver transplantation for perihilar cholangiocarcinoma.
Authors: Loveday Benjamin , Knox Jennifer J. , Dawson Laura A. , May Gary , Metser Ur , Brade Anthony M. , Horgan Anne M. , Cummings Bernard , Grant David , Gallinger Steven , Greig Paul David , Moulton Carol-anne 
Published: February 2017

394 Background: Neoadjuvant chemoradiation and liver transplantation is an option for selected unresectable patients with early stage perihilar cholangiocarcinoma (pCCA). This study aimed to determine the dropout rate, morbidity and survival of patients who entered a modified tri-modality protocol at Princess Margaret Cancer Centre. Methods: All patients enrolled into the protocol (Jan 2009 – Aug 2015) were included in the analysis. Enrollment criteria: ≤ 65 years old with brush biopsy-proven, unresectable pCCA proximal to the cystic duct, < 3.5 cm in diameter. Neoadjuvant protocol consisted of conformal radiation therapy (54-75 Gy, 1.5 Gy BID) concurrent with Capecitabine 800 mg/m2 BID until radiation completion. Following surgical staging patients received maintenance chemotherapy (Cisplatin 25 mg/m2 and Gemcitabine 1000 mg/m2, day 1 and 8 of 21 day cycle), until transplant or progression. Intention to treat analyses were performed on prospectively collected data to determine time to progression (TTP), dropout rate, overall survival (OS), and number of biliary procedures. Results: Seventeen patients were enrolled, with a median age of 53.9 (26.7-62.8) years, and tumour diameter of 2.7 (2.0-3.4) cm. Five patients had primary sclerosing cholangitis. Median follow up was 14 (6-41) months. The cohort required a median of 3 (0-8) biliary stents, and percutaneous transhepatic biliary drainage in 11/17. Median TTP was 6 (2-16) months. Protocol dropout occurred in 10/17 due to metastatic disease identified during chemoradiation (2), surgical staging (6), or maintenance chemotherapy (2). No dropouts were due to neoadjuvant toxicity. Four patients underwent transplantation (two living donor, two deceased donor), and three are on the transplant waiting list. Median survival from first consultation and start of chemoradiation was 18.2 and 17 months, respectively. Conclusions: Neoadjuvant chemoradiation and liver transplantation for unresectable early stage pCCA is feasible, although dropout during the protocol is high. Less than half of patients who began the treatment protocol remained eligible for transplantation due to cancer progression or upstaging after surgical staging.
Splenic embolization as an alternative to surgical splenectomy for the restoration of blood counts suitable for effective chemotherapy in gastrointestinal malignancies (GIM).
Authors: Marsh Robert de Wilton , Alonzo Marc , Ferral Hector 
Published: February 2017

396 Background: Chemotherapy regimens used for GIM are often notably myelosuppressive and may also engender hypersplenism. This can result in platelet (plt) and/or absolute neutrophil counts (ANC) too low for the maintenance of required dose intensity or frequency. One successful approach to this problem is surgical splenectomy but this is both morbid and invasive. An alternative strategy uses super-selective embolization of the splenic arterial tree, which is performed as an outpatient, and is far better tolerated. The true efficacy of this technique is uncertain and the optimal patients (pts) for this procedure are not well defined. Methods: Between 11/2012 and 6/2015, pts with ECOG PS 0/1 currently on active therapy for GIM in our clinics, whose plts and/or ANC were consistently below threshold values for appropriate frequency or intensity of therapy, were referred to Interventional Radiology for splenic embolization. Selective catheterization of the splenic artery was achieved via a femoral approach. This was followed by super-selective catheterization of branches of the splenic artery, as distally as possible, with subsequent embolization using Embosphere particles (300-500 micron spheres). All pts received prophylactic IV antibiotics. Results: 10 pts were identified and referred and all were deemed suitable for embolization. The mean plt count prior to the procedure was 73,000 (39,000-167,000) and the mean ANC was 3.5 (1.3 – 5.3). Following one procedure in 9 pts and 2 procedures in 1 pt, the mean plt count rose to 175,000 (55,000-432,000) and the ANC to 7.2 (2.9 – 13.2) immediately, and to a maximum of 253,000 (76,000-511,000) and 9.3 (5.0 – 14.5) within one to two months.Splenic enlargement was noted in 6 pts (mean size 18.3 cm) prior to the procedure and was not present in 4 pts. Following embolization all patients were able to resume chemotherapy with previously effective doses and/or frequency. Conclusions: In our cohort of pts with GIM, splenic embolization was successful at restoring acceptable plt and/or ANC levels for the resumption of effective chemotherapy. Splenomegaly does not appear to be a prerequisite for success.
Outcomes in metastatic pancreatic adenocarcinoma (MPAC) patients treated with FOLFIRINOX (FFX)/FOLFOX(FX) and gemcitabine + nab-paclitaxel (NabG).
Authors: Schmidt Shannon Leah , Durkal Vipal , Pattali Jayavalsan Shinoj , Thomas James P. , Ritch Paul S. , Erickson Beth , Christians Kathleen K. , Tsai Susan , Evans Douglas B. , George Ben 
Published: February 2017

397 Background: Standard front line (FL) chemotherapy regimens for MPAC include FOLFIRINOX (FFX)/FOLFOX(FX) and Nab-paclitaxel plus Gemcitabine (NabG). Outcome data in patients treated with both FFX/FX and NabG has not been well characterized. We retrospectively reviewed our single institution experience in MPAC patients treated with FFX/FX and NabG in either sequence. Methods: All MPAC patients treated with FFX/FX or NabG, in either sequence, from 1/1/11 to 12/31/14 at the Froedtert and Medical College of Wisconsin (MCW) Clinical Cancer Center were identified and their charts reviewed. This study was approved by the Froedtert & MCW Institutional Review Board. Results: Among the 64 patients reviewed, median age at diagnosis was 62 years, 64.1% were male and 95.3% were Caucasian. Median Ca19-9 and CEA at diagnosis were 855 and 10.4 respectively. Liver, lung and peritoneal metastases were appreciated in 87.5%, 20.3% and 35.9% of patients. 37/64 (57.8%) patients received second line (SL) therapy. Response Rate (RR) with FFX/FX and NabG in both FL and SL therapy are summarized in the Table. The median Progression Free Survival (PFS) with FL therapy was 3.7 months and 3.5 months with SL therapy. Median overall survival (OS) of the entire cohort was 8.7 months. In patients who received 2 lines of therapy the median OS was 12.1 months. Median OS in patients who received only one line of therapy was 4.1 months. Conclusions: In patients with MPAC, sequential therapy with FFX/FX and NabG is both feasible and effective in either sequence. RR and DCR with these regimens, while modest, are acceptable in the SL setting. Patients who received two lines of therapy have a substantially better OS than patients who receive one line of therapy, suggesting a more favorable tumor biology in the former population. [Table: see text]
Outcomes of neoadjuvant chemotherapy versus chemoradiation among patients with resected pancreatic head adenocarcinoma.
Authors: Franko Jan , Hsu Harold W , Thirunavukarasu Pragatheeshwar , Frankova Daniela , Goldman Charles David 
Published: February 2017

398 Background: Increasing use of neoadjuvant therapy in pancreatic cancer has been reported. We compared patterns of practice and outcomes of neoadjuvant chemotherapy (nCHT) versus chemoradiation (nCRT) among pancreatic cancer pts receiving pancreaticoduodenectomy. Methods: National Cancer Data Base pancreatic head adenocarcinoma patients (pts) diagnosed between 2003 and 2011 treated by nCHT or nCRT followed by pancreaticoduodenectomy. Backward elimination logistic and Cox regression models were used. Primary outcome measures were 30-day and 90-day postsurgical mortality and overall survival; adjusted odds (aOR) & hazard ratios (aHR) and 95% confidence intervals (CI) are reported. Results: In all 1,432 pts received neoadjuvant treatment with nCHT (n = 523) or nCRT (n = 909). Odds of 30-day mortality were influenced by age (aOR 1.03, CI 0.99-1.06,p = 0.077), average annual resection volume of facility (aOR 0.98, CI 0.97-1.00, p = 0.135), and household income quartile (aOR 1.94, CI 0.97-3.90, p = 0.060), but not by delivery of RT, comorbidities, gender, insurance status or facility type. Odds of 90-day mortality were influenced by age (aOR 1.03, 1.01-1.05,p = 0.004), household income quartile (aOR 1.37, CI 0.87-2.16, p = 0.171), and delivery of nCRT (aOR 1.69, CI 1.04-2.74, p = 0.032), but not by average annual resection volume of facility, comorbidity, gender, insurance status or facility type. Survival odds were influenced by age (aHR 1.01, CI 1.00-1.02, p = 0.001), margin status (aOR 1.50, CI 1.27-1.77, p < 0.001), ypN status (aHR 1.45, CI 1.26-1.68), p < 0.001), adjuvant CHT (aHR 0.81, CI 0.69-0.94, p = 0.006), and nCRT (aHR 1.21, CI 1.04-1.40, p = 0.012). On average pts with nCHT as compared to nCRT lived longer (median OS 26.4 vs. 24.2 months, p = 0.001; actuarial 3 yr 58% vs 49%, and 5 year survival 30% vs 14%). Conclusions: There is no detectable difference in early outcome (30-day postsurgical mortality) among pancreaticoduodenectomy pts treated with nCHT or nCRT. Trend toward a more favorable long-term outcome (30-day postsurgical mortality and overall survival) among those with nCHT without radiation is noted. Further studies with more detailed data sources are needed.