bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC).
Authors: Keskin Serkan , Sen Fatma , Aydogan Fatma , Ekenel Meltem , Kilic Leyla , Saglam Sezer , Sakar Burak , Disci Rian , Aykan Faruk 
Published: March 2020

e14628 Background: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy naïve AGC patients. Methods: Patients (n=54) with locally inoperable or distant metastasis, and performance status of 0–2 were eligible. The triplet combination chemotherapy consists of docetaxel 60 mg/m2 day 1, cisplatin 60 mg/m2 day 1, 5-flourouracil 600 mg/m2 for 5 days continuous infusion were administered every 21 days, up to 9 cycles. Prophylactic G-CSF was not allowed. Two of the patients treated with second line cisplatin/capecitabine. None of the patients treated with radiotherapy. Results: In all, 36 (67%) patients were male and 18 (33%) were female; median age was 59 years (range: 23-80 years). Majority of patients (n=46, 85%) were metastatic disease and 8 (15%) of them were locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (%43) and 18 (39%) of the 46 cases, respectively. The median cycle of chemotherapy was 6 (ranging from 1 to 9 cycles). In assessing fifty patients for response evaluation, one had complete response. The partial responses achieved in 27 (54%) patients. Seventeen patients (34%) had stable disease and 5 (10%) progressed. Of 2% (n=4) and 11% (n=6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. One patient developed febrile neutropenia. Severe thrombocytopenia, hepatic and renal toxicity were not seen. During median follow-up time (8.1 months, range: 1.3-24), 28 (52%) patients were died. The overall and progression-free survival were 11.6 [95% CI: 10.2-13] and 7.7 [95% CI: 6.8-8.7] months, respectively. Conclusions: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as original DCF in AGC with acceptable and manageable side effects.
Stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma with Child-Pugh class B.
Authors: Cardenes Higinia Rosa , Lasley Foster D , Kwo Paul , Perkins Susan M. , Maluccio Mary A. 
Published: March 2020

e14683 Background: Stereotactic body radiotherapy (SBRT) is a promising therapeutic modality in hepatocelular carcinoma (HCC). A Phase I trial was conducted at Indiana University (IU) in patients with Child Pugh Class (CPC) A and B. Based on our results, patients with CPC-B patients with score <=7 continued enrollment in the phase II. We now present an interim analysis for this patient population. Methods: 14 patients with HCC with liver cirrhosis, CPC-B, were treated with SBRT in a Phase I-II trial at IU. All patients were scheduled to receive five fractions, 800 cGy per fraction (total dose 4000 cGy), 1-2 fractions per week. Dose was prescribed to the 80-90% isodose line covering the planning target volume (PTV). A modified RECIST criterion was used to determine local failure. Demographics, clinical variables, treatment –related toxicities within 90 days of end of treatment, and local control (LC) at 6 and 12 months were tabulated. Progression Free Survival (PFS), Time to Progression (TTP), and Overall Survival (OS) estimates were calculated using Kaplan-Meier methodology. This was an unplanned interim analysis. A formal interim analysis will take place later. Results: There were 13 males and 1 female; median age of 56.5 years (range 49-69). All patients had 1 treated lesion. Median (range) for gross tumor volume (GTV) (cc) was 40.1 (8.0-74.6); PTV volume (cc) was 120.1 (34.7-210.0); and uninvolved liver volume (cc) was 2137.9 (973.0-2796.0). There were 3 grade 4 toxicities, 1 each of hyperbilirubinemia, hypokalemia, and thrombycytopenia. Four patients underwent orthotopic liver transplant. Local control at 6 and 12 months were 90% [95% C.I. (55.5%, 99.8%)] and 87.5% [95% C.I. (47.4%, 99.7%)], respectively. Median PFS is 11.0 months (95% CI: 3.9 months, 17.4 months). Ten patients died or progressed including 4 patients who died without progressing. Median TTP is 17.4 months (95% CI: 5.3 months, upper limit not estimable). Median OS is 19.8 months (95% CI: 4.0 months, upper limit not estimable). Conclusions: in carefully selected patients with hepatocellular carcinoma in the context of CPC B liver cirrhosis, score less or equal than 7, SBRT is an effective therapy with a good toxicity profile. Phase II is ongoing.
Antitumor efficacy and pharmacokinetics of a novel gemcitabine oral formulation (INNO-D07001) in xenograft animal models.
Authors: Hsu CS , Hao W-H , Wang J-J , Lin T-H , Kuo R-Y 
Published: March 2020

e14699 Background: INNO-D07001 is a novel oral gemcitabine formulation which was developed to enhance the oral bioavailability of gemcitabine and it has been successfully demonstrated in both beagle dogs as well as nude mice. The objectives of this study were to examine the antitumor activity of this novel gemcitabine oral formulation in human xenograft models of pancreatic tumors with different daily doses as well as various dosing schedules. Methods: The INNO-D07001 dosing solutions (gemcitabine oral formulation) were formulated freshly before treatment and water for injection (USP) was used as the diluent. There were seven groups in the study and it was ten female NCr-nu/nu mice (with human CFPAC-1 pancreatic tumor) per group. Two doses (5 mg/kg and 10 mg/kg) and three dosing schedules (Q1D, Q2D, and Q3D) were examined. Water for injection (by oral administration) was used as the blank control and Gemzar (180 mg/kg by I.V.) was used as the active control. All INNO-D07001 dosing solutions were administered to mice by P.O. and, on the other hand, Gemzar was administered to mice by I.V. All animals were designed to receive doses for 12 days based on different doses and dosing schedules. Total body weights and tumor sizes were recorded continuously for evaluating the toxicity and antitumor activity, respectively, of INNO-D07001. Results: Oral administration of INNO-D07001 once daily at doses of 10 and 5 mg/kg/dose was not tolerated. In contrast, oral administration of INNO-D07001 on a Q2Dx6 schedule at a dose of 10 mg/kg/dose and on a Q3Dx4 schedule at doses of 10 and 5 mg/kg/dose was well tolerated. Moreover, the INNO-D07001 treatment at a dose of 10 mg/kg/dose on a Q2Dx6 schedule produced statistically significant inhibition of tumor growth (i.e. more than 60% inhibition rate comparing to the blank control) on the last treatment day. Conclusions: The novel gemcitabine oral formulation (INNO-D07001) is well tolerated and effective at a dose of 10 mg/kg/dose on a Q2Dx6 schedule to show the significant inhibition of pancreatic tumor growth. Future preclinical study in toxicity evaluation with repeating doses is ongoing in order to provide adequate safety information before entering phase I clinical study.
Gemcitabine (G) plus nab-paclitaxel (nab-P) plus chemoradiation (CRT) in locally advanced pancreatic cancer (LAPC).
Authors: Olowokure Olugbenga Olanrele , Bedoya Ivan Dario , Mierzwa Michelle Lynn , Torregroza Maria Patricia , Dwivedi Alok kumar , Wang Jiang , Smith Milton T , Schmulewitz Nathan , Kucera Stephen , Choe Kyuran Ann , Ristagno Ross , Rudich Steven , Sussman Jeffrey J. , Ahmad Syed A 
Published: March 2020

e14714 Background: 30-40 % of PC pts present with LAPC. Optimal management remains controversial. Current NCCN guidelines, suggests clinical trial, FOLFIRINOX, G, G based combination therapy, chemo followed by CRT as options in pts with good PS. This single institution retrospective review, evaluated the UC experience of the impact of G+nab-p+/- CRT in LAPC. Methods: From 05/01/09-09/01/11,105 newly registered pts were identifiedusing ICD code 157, 13pts met inclusion criteria: ECOG PS 0-2, histologically proven LAPC, without prior therapy that received G + nab-P, pre or post radiation as part of their treatment. G+nab-p was given as cycles of G=1,000mg/m2 and nab-P=100mg/m2 weekly x3 every 4 weeks with appropriate modifications. CT scans and CA19-9 levels were followed. PFS was estimated from the date of diagnosis to date of progression or death if this occurred first and OS was estimated from date of diagnosis until date of death or loss to follow up. Kaplan Meier survival estimates were obtained with 95% confidence interval (CI). Log rank test was used to compare the PFS according to categorical variables. Results: Median duration of follow up was estimated to be 14.4 months (M) range(R) (5.8-19). CA19-9 data was available for 12 pts, 2 had baseline <1 (R<1-12,861), CA19-9 decrease > 50% from baseline was seen in 9/10. Mean # of G+nab-P cycles administered was 3, R (1-10). 77% received G based CRT with only 1pt receiving this post op. 38% (5/13) underwent resection, 4 post CRT with R0 margins and -ve LN’s and 1 pre CRT with R0 margins but 1/13 LN’s +ve. 11 pts were evaluable for response by RECIST (4PR, 6SD, 1PD). Disease control rate 91%. PFS 92% (CI: 57- 99%) at 6 M and 65% (CI: 31-85%) at 12 M. OS was 85% (CI: 51-96%) at 6M and 77 %(CI: 44-92%) at 12M. At 6M, 100% PFS was observed in resected group, whereas 88% PFS in non-resected group (p=0.12). There was no significant difference in PFS according to gender (p=0.44) and T lesion (p=0.49). Grade III/IV toxicity was mainly hematologic and gastrointestinal. (4/7) 57% received further therapy upon progression. Conclusions: Compared to contemporary G- based trials, the UC experience of G+ nab-P with CRT appears to be associated with improved survival in LAPC and warrants further study.
Single center experience of perioperative EOX in locally advanced resectable gastroesophageal cancer (GEC).
Authors: Djanani Angela , Pall Georg , Bechter Oliver Edgar , Kafka-Ritsch Reinhold , Zitt Matthias , Pratschke Johann , Kasseroler Marie-Therese , Eisterer Wolfgang 
Published: March 2020

e14719 Background: Perioperative chemotherapy has shown to improve local control and survival in GEC (MAGIC, FFCD, EORTC40954) deploying 5-FU and cisplatin ± epirubicin. A triple chemotherapy with EOX (epirubicin, oxaliplatin, capecitabine) showed a promising response rate and an improved outcome in stage IV disease (REAL2). Methods: We analyzed 24 patients with locally advanced GEC (uT2N+, uT3N0-3, UICC II-IV) treated in our institution from 2008 to 2011 who received neoadjuvant EOX (epirubicin 50mg/qm iv d1 qd22, oxaliplatin 130mg/qm iv d1 qd22, capecitabine 1650mg/qm daily) followed by surgery followed by adjuvant EOX. The aim of this study was to retrospectively analyze the efficacy and toxicity of perioperative EOX and the treatment efficacy. Results: We treated 6 (25%) females and 18 (75%) male patients. Stage distribution was 42% UICC stage II, 50% stage III and 8% stage IV (cT1-4N3M0). All patients received neoadjuvant EOX. Dose reductions were necessary in 4/24 patients (17%). No treatment related deaths occurred. Main toxicities were grade 3/4 leucopenia 4/24 patients (17%), thrombopenia 2/24 patients (8%), diarrhea 3/24 patients (12%, CTC criteria 2.0). One patient suffered from a myocardial infarction after the third cycle of chemotherapy. Progression of disease was observed in 2 patients (8%). Surgery was performed in 21/24 patients (88%) with R0-resection rate of 100%. We recorded no major surgical complication. Downstaging assessed by histopathological response was achieved in 10 patients (48%) with complete pathological remission (CPR) in 2 patients (10%). 10 patients (42%) received adjuvant therapy. 54% of the patients are still alive and in complete remission. after a follow up period of 2 years. One patient died because of a cardiac arrest 2 weeks after surgery. Conclusions: Preoperative chemotherapy with EOX causes moderate toxicity and is associated with a meaningful clinical activity. The significant downstaging in locally advanced GEC suggests that this regiment is highly active in locally advanced gastric cancer. According to our experience EOX represents a valid alternative to cisplatin and 5FU ± epirubicin chemotherapy in curatively treated GEC.
Image-guided targeted intraarterial delivery of chemotherapy drug loaded iron oxide nanoparticles to rabbit liver cancer model.
Authors: Kim Hyun Sik , Lawal Taoreed O , Prieto Veronica E , Huang Jing , Wang Liya , Mao Hui 
Published: March 2020

e14734 Background: To develop an enhanced drug delivery system to liver tumors using novel MRI traceable iron oxide nanoparticles (IONP) loaded with doxorubicin and to investigate biodistribution of deliverednanoparticle and by assessing intratumoral and normal liver tissue concentrations after targeted (IA) versus systemic (IV) administration. Methods: Paramagnetic IONP (core and hydrodynamic size of 10 nm and 23 nm, respectively) coated with amphiphilic polymers were non-covalently loaded with hydrophobic doxorubicin; whose presence was confirmed by optical absorption spectrum. VX2 liver tumors were induced in the left lobe of 12 rabbits, allowed to grow for 2 weeks to a size of 2 cm, and were subsequently divided into 2 treatment groups, each receiving 1 mg/kg body weight of doxorubicin via IONP. Group 1 received IA administration to the left hepatic artery under fluoroscopy, and Group 2 received IV administration via the marginal ear vein. Animals were sacrificed 24 hours after treatment. Tumor and liver sections were collected and iron concentrations of tumor and liver tissues were determined by the colorimetric method with iron binding 1,10-phenanthroline at 508 nm. Analysis of tissue iron concentrations in different groups was performed using a standard t-test, with p<0.05 considered significant. Results: Intratumoral and peritumoral concentrations of IONP were significantly higher 24 hours after IA administration than IV (1.54 vs 1.03 mg Fe/g , p=0.019), given at the same dosage. Additionally, 24 hours after treatment, the group receiving IA therapy showed significantly higher nanoparticle concentrations in the left hepatic lobe in comparison to the IV group (1.63 vs 1.34 mg Fe/g, p=0.0226). Conclusions: Targeted IA delivery significantly enhances intratumoral and peritumoral uptake of IONP when compared to IV. Targeted intraarterial delivery of IONP carrying doxorubincin can serve as a powerful tool in serving as a vehicle to deliver chemotherapy drugs to liver tumors. To further evaluate the potential of this drug delivery method, future studies will correlate the biodistrubution of the IONP to drug concentrations and findings on histology, imaging, tumor response.
Phase II trial of tamoxifen for progressive advanced urothelial carcinoma following prior chemotherapy.
Authors: Lerner Seth P. , Sternberg Cora N. , Younes Mamoun , Calabro Fabio , Cerbone Linda , Chandrashekar A , Mitchell Carmen , Shen Steven S. , Sonpavde Guru 
Published: March 2020

e15003 Background: Urothelial carcinoma (UC) expresses estrogen receptor (ER)-β, which increases with stage and grade. The selective estrogen receptor modulators, tamoxifen and raloxifene have displayed anti-tumor activity in preclinical UC. Effective therapy for progressive UC following chemotherapy is lacking. A rationale can be made to evaluate the activity of tamoxifen following prior chemotherapy for advanced UC. Methods: A non-randomized two-center 2-stage phase II trial was planned. Eligible patients were required to have bladder or upper tract urothelial cancer, measurable metastatic disease, 1-2 prior chemotherapy regimens, adequate organ function and ECOG performance status (PS) 0-2. The primary endpoint was freedom from progression (FFP) at 4 months (mo), with secondary endpoints of response, survival, toxicities and association of tumor ER studies with FFP. FFP of ≥30% was considered important and ≤10% was felt to reflect poor activity. Twenty-five evaluable subjects were required, 15 during stage 1 and 10 during stage 2 for α=0.05 and power =0.8. If ≥2 patients attained FFP during stage-1, the trial proceeded to stage-2. Tamoxifen was administered as 20 mg orally once daily until progression by RECIST or intolerable toxicities. Clinical assessments were performed every 4 weeks and imaging every 8 weeks or earlier if indicated. ER isoforms were measured in archival formalin fixed tumor. Results: The trial has completed accrual with 28 patients enrolled of whom 18 are currently evaluable (16 male and 2 female). Number of prior chemotherapy regimens was 2 in 15, ≥3 in 2 and unknown in 1 patient. ECOG-PS was 0 in 9, 1 in 7 and 2 in 2 patients. Liver metastasis was present in 4 and anemia (Hb <10 gm/dL) in 7 patients. Four patients (22.2%) attained FFP at 4 mo. Minor tumor regression was seen in 1 patient. One grade 3 toxicity (deep vein thrombosis) possibly related to therapy was observed. Tumor ER isoform studies and correlation with FFP will be presented. Conclusions: Tamoxifen exhibited potential activity in a subset of patients with advanced UC following chemotherapy. Given the excellent tolerability, further study may be warranted to identify factors predictive of benefit in less heavily pretreated patients.
Urothelial cancer: Gender discrepancies and impact on overall survival.
Authors: du Manoir Jeanne Michelle , Richter Sue , Sridhar Srikala S. 
Published: March 2020

e15020 Background: Gender differences for disease course and survival in various cancers exist. Gender disparity for both stage at diagnosis and overall survival (OS) has been observed in urothelial cancer (UC). We report a single institution analysis of UC patients treated with chemotherapy to further investigate gender differences in outcomes. Methods: We identified 190 bladder cancer pts treated with chemotherapy (adjuvant of palliative) since 2002. Age and stage at diagnosis, sex, smoking status, radiation/chemical exposures, bloodwork as a measure of organ dysfunction, ECOG performance status (PS), pathology, chemotherapies, presenting symptoms, other malignancies, and survival info was collected. Baseline demographics were compared by z test for significance and outcomes using chi square statistic. Survival was determined by censored Kaplan-Meier methods. Results: Average age and stage at diagnosis, and PS were similar for both genders. Males had significantly more exposure to smoking (58% vs 48%, p<0.05) and radiation/chemical exposures (28% vs 10%, p<0.05). Invasive urothelial carcinoma was the predominant histological diagnosis for both genders, but males were found to have significantly more subtypes or other pathologies (22.2% vs 14%, p<0.05). Males were found to have more malignancies diagnosed prior to or concurrently with their UC diagnosis (27.8% vs 20%, p<0.05). Standard Gem-Cis was given more often to males (70% vs 49%, p<0.01) despite no differences in age, organ dysfunction or PS between genders. Receiving alternative chemotherapy in the first-line setting was associated with a poorer 3-year OS (p<0.05) for either sex, as was stage of diagnosis, presence of visceral disease, creatinine, and ECOG PS (p<0.05). Conclusions: Our data suggests that poorer outcomes in females was associated with not receiving standard chemotherapy (Gem-Cis) as frequently as males, despite similar baseline characteristics. Both males and females had significantly improved OS when they received Gem-Cis as the first regimen of chemotherapy. This study reinforces the importance of administering cisplatin as initial chemotherapy to improve outcomes in UC.
Stage I seminoma: Treatment outcomes in a low-income country.
Authors: Abuodeh Yazan Asad , Abdelrahman Fadwa , Salem Ahmed Abdel-Fattah , Farah Naim , Al-Mousa Abdelatif , Khader Jamal 
Published: March 2020

e15024 Background: The aim of this report is to address treatment outcomes of patients with early-stage seminoma in a developing country with special reference to patients with history of surgical violation of the scrotum and the potential predictors of disease relapse. Methods: Seventy four patients with pure seminoma were treated at King Hussein Cancer Center (Amman, Jordan) between 2003 and 2010. All patients underwent orchiectomy. All but 3 patients received adjuvant radiotherapy. Patients who underwent surgical violation of the scrotum prior to referral were managed by further excision or irradiation of the scrotal scar. The follow-up ranged from 1 to 200 months (mean, 33 months). Results: At the time of follow-up; all but one patient remain alive. The 3-year relapse-free survival for the entire cohort was 95.9%. Three patients were burdened by relapse, all of whom received adjuvant irradiation following inguinal orchiectomy and initially harbored tumors larger than 4cm upon pathological examination. Median time to relapse was 14 months (range, 8-25 months). None were associated with elevated tumor markers prior to detection of relapse. All but one patient were successfully salvaged by chemotherapy. Conclusions: Our results confirm the excellent prognosis for patients with early-stage seminoma treated by orchiectomy and adjuvant radiotherapy in a developing country. Although all patients burdened by relapse demonstrated adverse pathological findings upon initial assessment, no consistent predictor of relapse was found. Scrotal scar re-excision or irradiation in patients with prior history of surgical violation of the scrotum are effective in preventing local failure.
PAPR1 expression in testicular germ cell tumors.
Authors: Mego Michal , Cierna Zuzana , Svetlovska Daniela , Macak Dusan , Machalekova Katarina , Miskovska Viera , Chovanec Michal , Usakova Vanda , Babal Pavel , Mardiak Jozef 
Published: March 2020

e15027 Background: Testicular germ-cell tumours (TGCTs) represent a model for the cure of cancer. Nonetheless, a small proportion of patients develop disease recurrence. PARP inhibitors represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate poly(ADP-ribose)polymerase-1 (PARP1) expression in TGCTs and to correlate expression patterns with clinico-pathological variables. Methods: In this translational study, tumor specimens from 124 patients with GCTs were identified. PARP1 expression was detected by immunohistochemistry using monoclonal antibody, scored by the multiplicative quickscore (QS) method and compared to PARP1 expression in testicular tissue of normal testis. The QS was calculated by multiplying the percentage score by the staining intensity score to yield a minimum value of 0 and a maximum value of 18. Based on the QS nuclear PARP1 expression was graded as low (0–9) or high (10–18). Results: We observed higher expression of PARP1 in testicular tumors compared to normal tissue of testis (mean QS = 10.04 vs. 3.60, p < 0.0000001). Mean QS ± SD for each histological subtype was following: intratubular germ cell neoplasia (ITGCN) = 18.00 ± 0.00, embryonal carcinoma = 9.62 ± 5.64, seminoma = 9.74 ± 6.51, yolc sac tumor = 7.8 ± 7.20, teratoma = 5.87 ± 5.34, and choriocarcinoma = 4.50 ± 8.33. The PARP1 overexpression (QS > 9) was most often detected in ITGCN (100% of specimen with PARP1 overexpression), seminona (52.6%), embryonal carcinoma (47.0%), yolc sac tumor (33.3%), teratoma (26.7%), and choriocarcinoma (25.0%), compared to 1.9% of normal testicular tissue specimen. There was no association between PARP1 expression and clinical variables. Conclusions: PARP1 overexpression is an early event in the development of TGCTs. We suggest that PARP1 could represent a novel treatment target in TGCTs and the assessment of PARP1 expression in tumor samples may lead to the consideration of TGCTs patients for PARP inhibitor therapy.