bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II breast cancer chemoprevention study of lovastatin in high-risk women: Initial feasibility data
Authors: Kurian A. W. , Sharma V. B. , Schwartz E. J. , Mills M. A. , Staton A. D. , Chun N. M. , Kingham K. E. , Ford J. M.
Published: March 2020

1502

Background: More than 250,000 U.S. women have high inherited breast cancer risk; many develop hormone-receptor negative (ER/PR-) tumors, for which no chemoprevention exists. Pre-clinical data suggest that hydrophobic HMG-CoA reductase inhibitors (statins) may reduce risk of ER/PR- breast cancers. We report initial feasibility results of a phase II study of lovastatin for breast cancer chemoprevention. Methods: Study Design: Single-arm, non-randomized phase II study. Agent: Lovastatin 80 mg daily for 6 months. Primary Endpoint: Change in proportion of women with atypical cytology on 2-quadrant random periareolar fine needle aspiration (rpFNA) of breast duct cells before and after lovastatin. Secondary Endpoints: Changes in Ki-67, ER/PR, and elevated levels of oxidative DNA damage (ODD) measured by single-cell gel electrophoresis (Comet) assay of breast duct cells; changes in mammographic density; breast cancer incidence. Eligibility: BRCA1/2 mutation carrier, or estimated lifetime risk = 20% due to family history. Statistical Considerations: Planned sample size of 60, yielding 90% power to detect 50% change in proportion with atypia. Results: Twenty participants enrolled in Year 1; 15 have pre-study rpFNA and 5 have post-study rpFNA results to date. Pre-Study Cytology: N=15: 1 (7%, 95% confidence interval 0–32%) had insufficient, 11 (73%, 48–90%) had normal, and 3 (20%, 6–46%) had atypical cytology. Pre-Study Comet Assay: N=4 to date, 2 with atypical and 2 with normal pre-study cytology: 2 with atypical cytology (100%, 29–100%) had a positive Comet assay for elevated ODD, but 0 with normal cytology (0%, 0–71%) had a positive Comet assay. Post-Study Cytology: N=5, 1 with atypical cytology pre-study: 5 (100%, 51–100%) were normal post-study. Post-Study Comet Assay: N=1 to date, with atypical cytology and positive Comet assay pre-study: cytology was normal and Comet assay negative post-study. The study has been well-tolerated, with no drop-out. Conclusions: An early-stage chemoprevention study of lovastatin for 6 months, including 2 rpFNAs, appears feasible in high-risk women. Early results suggest a correlation between cytologic atypia and elevated levels of ODD, and the possibility that lovastatin might reverse these abnormalities. Accrual is ongoing.

No significant financial relationships to disclose.
Vinflunine in patients with advanced unresectable hepatocellular carcinoma and liver impairment
Authors: Saliba F. , Paule B. , Adam R. , Castaing D. , Azoulay D. , Ogier I. , Pinel M. , Cadic V. , Delgado M.
Published: March 2020

15023

Background: In patients (pts) with advanced hepatocellular carcinoma (HCC) and liver cirrhosis, systemic chemotherapy has most commonly been associated with a very low response rate and high toxicity leading to death from liver failure. Vinflunine (VFL) is a new microtubule inhibitor of the vinca alkaloid class which has demonstrated clinical activity in several tumour types. Methods: A phase I trial was designed to determine VFL dose adjustments in cancer pts with various degrees of liver dysfunction. A high number of pts with HCC and concomitant liver cirrhosis (Child-Pugh grades A and B) were included in the study (18/30 pts). Therefore, a subgroup analysis was carried out in order to determine the safety profile of VFL in these pts (NCI-CTC version 2.0) and to estimate its anti-tumour activity (WHO criteria). Results: Eighteen pts (15 males) of median age 60.7 [26.4–75.3] years with advanced stage and unresectable HCC were treated with VFL. All these pts were outside Milan criteria and ineligible for liver transplantation. Thirteen pts had been previously treated by chemotherapy. The WHO performance status was 0: 11 pts, 1: 5 pts, 2: 2 pts. They received a median number of 4 cycles [1.0–31.0] of different doses of VFL according to the severity of the underlying liver impairment 320 mg/m2 (3 pts), or 250 mg/m2 (6 pts) or 200 mg/m2 (9 pts). One partial response (PR) was observed while 11 pts (61.1%) had stable disease (SD) yielding a disease control rate (PR + SD) of 66.7%. The median progression free survival was 3.4 months [95% confidence interval (CI): 2.6–6.0]. Haematological toxicity: grades (G) 3 anaemia = 4 pts, G3/4 neutropenia = 11 pts, G3 thrombocytopenia = 7 pts, no febrile neutropenia. Other G3 toxicities included G3 abdominal pain (2 pts), constipation (3 pts), neutropenic infection (1 pt). Six pts experienced G3 (5 pts) or 4 (1 pt) fatigue. Conclusions: Vinflunine can be given safely at 320 mg/m2 or 250 mg/m2 or 200 mg/m2 in pts with unresectable advanced HCC with different degrees of liver impairment. The disease control rate is promising (66.7%).

No significant financial relationships to disclose.
Treatment with bevacizumab (BEV) upregulates expression of the transcription factor Sp1 and its downstream target genes in human carcinoid cells: Molecular basis of the synergistic antiangiogenic activity of bevacizumab and mithramycin A (MIT)
Authors: Zhang J. , Jia Z. , Wang L. , Li Q. , Xiangdong L. , Xie K. , Yao J. C.
Published: March 2020

15031

Background: Our previous studies show that human carcinoid cells overexpress pro-angiogenic factors, vascular endothelial growth factor A (VEGF), and transcription factor Sp1 plays a critical role in VEGF inducible and constitutive expression. However, the impact of antiangiogenic therapy on the Sp1/VEGF pathway remains unclear. Method: Groups of 10 athymic BALB/c nude mice were implanted with 1.5 million human H727 carcinoid cells. Treatment with VEGF neutralizing monoclonal antibody, BEV, MIT, or BEV + MIT was initiated once implanted tumor reached 4 mm in size. Result: Treatment with BEV, suppressed human carcinoid growth in nude mice (tumor size at week 5 1280 mm3 vs 480 mm3; p < 0.001). Gene expression analyses revealed that this treatment substantially upregulated the expression of Sp1 (7 folds) and its downstream target genes, including VEGF (5 folds) and epidermal growth factor receptor (4 folds), in tumor tissues, whereas it did not have this effect on carcinoid cells in culture. Treatment with mithramycin A, an Sp1 inhibitor, suppressed the expression of Sp1 and its downstream target genes in both cell culture and tumors growing in nude mice. Median survival of mice treated with PBS, BEV, MIT, and BEV + MIT groups were 88, 112, 121, and >160 days respectively (p < 0.001). Combined treatment with bevacizumab and mithramycin A produced synergistic tumor suppression, which was consistent with suppression of the expression of Sp1 and its downstream target genes. Conclusion: Treatment with bevacizumab may block VEGF function but activate the pathway of its expression via positive feedback. Given the fact that Sp1 is an important regulator of the expression of multiple angiogenic factors, bevacizumab-initiated upregulation of Sp1 and subsequent overexpression of its downstream target genes may affect the potential angiogenic phenotype and effectiveness of antiangiogenic strategies for human carcinoid.

No significant financial relationships to disclose.
Late term renal complications related to chemoradiotherapy in patients with gastric cancer
Authors: Mayadagli A. , Seseogullari O. O. , Gemici C. , Ozkan A. , Parlak C. , Gocen E.
Published: March 2020

15033

Background: The aim of this study is to evaluate late term renal complications of the combined treatment with chemoradiotherapy, according to the scheme of McDonald et al, in patients diagnosed with gastric cancer, after radical curative surgery. Methods: Totally 44 patients who administered to our clinic between years 2003 and 2004, with the diagnosis of gastric cancer, and with the age-adjusted creatinine clearance test (CCT) results within normal range, were enrolled into the study. Surgical procedure was subtotal gastrectomy in 34 patients (63,6%), and total gastrectomy in 16 patients (36,4%). Total 4600 cGy radiotherapy was administered to all patients through parallel-opposed AP-PA fields in 23 fractions concomitant with chemotherapy according to the scheme of McDonald et al. One year after the completion of the treatment, a technetium 99-m renal scintigraphy (DMSA) and CCT were performed to all patients whose renal functions were within normal limits. Results: Median age in the study was 52 (22–78). 34 patients (77,3%) were male and 10 (22,7%) were female. TNM stages were stage II in 15 (34,1%), IIIA in 21 (47,7%), IIIB in 4 (9,1%), and IV in 4 cases (9,1%). CCT measured 1 year after the treatment was low in 13 patients (29,6%), and within normal range in 31 patients (70,4%). Renal scintigraphy revealed damage at one pole in 32 patients (72,7%), damage at bilateral renal poles in 8 patients (18,3%), and it was normal in 4 patients (9%). Renal damage was higher in left kidneys than right kidneys (89,9% vs. 15,4%). There was a correlation between CCT values and scintigraphical findings. Damage in bilateral renal poles was higher in cases with low CCT than in cases with normal values (85,7% vs. 15,4). In general, there were no statistically significant relationship between late term renal complications and sex, and grade III treatment-related gastrointestinal toxicity. However, the relationships with age, extent of surgery reached statistical significance (p=0.009, and =0.006). Renal damage was notably higher in older patients, and in patients who underwent total gastrectomy. Conclusions: Since postoperative chemoradiotherapy is a novel modality for the treatment of gastric cancer, more studies are required in order to evaluate chronic toxicities.

No significant financial relationships to disclose.
Combination treatment of paclitaxel, cisplatin and infusional 5-fluorouracil (PCF) as first-line chemotherapy for metastatic or recurrent gastric cancer: Prospective multicenter clinical trial
Authors: Jin M. , Zhang X. D. , Shu Y. Q. , Liang J. , Yang J. W. , Chen L. , Cao W. G. , Shi G. M. , Guo C. Y. , Zhang F. C.
Published: March 2020

15035

Background: Paclitaxel has been shown to be effective in patients with advanced gastric cancer. We assess the combination of paclitaxel (Anzatax®, Mayne Pharma), infusional 5-fluorouracil and Cisplatin as first-line chemotherapy for metastatic or recurrent gastric cancer. Methods: Patients with previously untreated metastatic gastric adenocarcinomas are eligible. Fifty patients received paclitaxel (Anzatax®, Mayne Pharma) 150mg/m2 by 2-hour infusion day 1, cisplatin 15 mg/m2 daily days 1 through 5, and 5- fluorouracil by continuous infusion at a dose of 600 mg//m2 daily days 1 through 5. Cycles were repeated every 3weeks until progression. Objective tumor responses, duration of response, time to progression, and toxicity profile are the end points evaluated in this study. Results: Total 50 patients were enrolled (41 men, 9 women). The median age was 59 years (range 32 - 75). All patients had ECOG performance status (PS) 0–2 and adequate organ functions. 50 patients completed one-six cycles (mean 3 cycles). Forty-four patients were evaluable and all patients were assessable toxicity. In these 44 assessable patients, 1 CRs and 14 PRs were obtained, resulting in an overall response rate of 34%. 19 patients (43.2%) had stable disease, and 3 patients (8.9%) progressed. The tumor control rate was 77.3%. The median time to progression(TTP) was 5 months. The major (Grade 3–4) toxicities were neutropenia (22%) and anorexia (4%). There were no treatment-related deaths were recorded in all patients. The median and overall survival times are now being followed up and the results will be announced during the ASCO 2007 annual meeting. Conclusion: The combination of paclitaxel (Anzatax®, Mayne Pharma), cisplatin,and 5-FU has substantial antitumor activity in advanced gastric cancer. The toxicity of this regimen is within acceptable range, but no remarkable response rate was noted. Paclitaxel is an important new agent in the treatment of gastric cancer, and further evaluation of this agent in combination chemotherapy is warranted.

No significant financial relationships to disclose.
Pancreatic neuroendocrine tumors: Can the WHO staging system be simplified
Authors: Ferrone C. , Tang L. H. , Tomplinson J. , Klimstra D. S. , Coit D. G. , Brennan M. F. , Allen P. J.
Published: March 2020

15038

Background: The current World Health Organization (WHO) classification system for well-differentiated pancreatic endocrine neoplasms (PENs) is complex, and incorporates both stage- and grade-specific information. The aim of this study was to compare separately the prognostic value of stage and grade in a large single institution study of PENs. Methods: A prospectively maintained database from a single institution identified 183 patients who underwent operative treatment for a PEN between 1982–2005. Tumors were staged (<2 cm primary, =2 cm primary, metastatic disease) and graded (Low: no necrosis and <2 mitoses/50 high-power fields - HPF. Intermediate: presence of necrosis and/or =2 mitoses/50 HPF) with a simplified schema. The influence of tumor stage and grade on disease recurrence and disease-specific survival (DSS) was assessed. Results: Median age of the 183 patients was 56 years and 53% were women. Median length of follow-up was 44 months. At the time of presentation 35 patients (19%) had tumors <2 cm without evidence of metastatic disease (<2 cm), 96 patients (52%) had tumors =2 cm without metastases (=2 cm), and 52 patients (29%) were found to have nodal or distant metastatic disease (mets). Size of the primary tumor was not associated with the presence of nodal metastases (mean diameter: N0, 4.8 cm vs. N1, 4.7 cm: p=0.96) and 5/19 patients with tumors =2 cm had positive nodes. Grade was determined in 98% of patients (n=180). Low-grade tumors were present in 102 patients (56%) and intermediate grade tumors in 78 patients (42%). Earlier stage tumors were more likely to have low grade disease (% Low grade: <2 cm, 83%; =2 cm, 61%; mets, 28%: p <0.001). For all patients, tumor stage and grade were associated with survival (5-yr DSS: Stage: <2 cm, 100%; =2 cm, 90%; mets, 70%: p<0.001. Grade: Low, 98%; Intermediate, 70%: p<0.001). For patients with tumors =2 cm or with mets, grade was associated with survival within each sub-group (5-yr DSS =2 cm: Low 97% vs. Intermediate 80%: p<0.001, Mets: Low 93% vs. Intermediate 62%: p=0.05). Discussion: Stage and grade are important independent prognostic factors in patients with PENs. More accurate prognostic information can be provided by combining tumor size and metastases with simple grading information based on necrosis and mitotic rate.

No significant financial relationships to disclose.
Phase II study of paclitaxel, cisplatin, and 5-FU combination chemotherapy in patients with advanced gastric cancer
Authors: Cho S. , Shim H. , Lee S. , Ahn J. , Yang D. , Kim Y. , Park C. , Lee J. , Chung I. , Kim H.
Published: March 2020

15052

Background: Taxane has been used widely in advanced gastric cancer, but toxicities are problematic. To avoid the bone marrow suppression, docetaxel could be replaced paclitaxel to reduce bone marrow suppression and to improve the efficacy, we planned to augmentation of the dose intensity. This phase II study evaluated the efficacy and safety of combination chemotherapy with paclitaxel, cisplatin, and 5-fluorouracil (5-FU) in advanced gastric cancer. Methods: Patients with histologically confirmed gastric adenocarcinoma, ECOG PS = 2, at least one measurable lesion and adequate organ functions were eligible. Paclitaxel (175 mg/m2) and cisplatin (75 mg/m2) were given as a 1-h intravenous infusion on day 1, followed by 5-FU (750 mg/m2) as a 24-h continuous infusion for 5 days. This cycle was repeated every 3 weeks. Results: Forty-five eligible patients (median age 56 years) were treated in this way. Of the 41 patients in whom efficacy was evaluable, an objective response rate (ORR) was seen in 20 (48.8%), a complete response in two, and a partial response in 18 patients. The median time to progression was 6.9 months (95% CI, 5.86–7.94), and the median overall survival was 13.1 months (95% CI, 8.83–17.37). The main hematological toxicity was neutropenia and greater than grade 3 neutropenia was observed in 67 cycles (25%). Febrile neutropenia developed in three patients (7.3%). The major non-hematological toxicities were asthenia and peripheral neuropathy, but grade 3 or 4 toxicity was not seen. Conclusions: The combination chemotherapy with paclitaxel, cisplatin, and 5-FU is a promising regimen, and was well tolerated in patients with advanced gastric cancer.

No significant financial relationships to disclose.
Radio-frequency ablation (RFA) is equivalent in therapeutic effect but safer compared to microwave coagulation therapy (MCT) for hepatocellular carcinoma
Authors: Beppu T. , Masuda T. , Ishiko T. , Hayashi H. , Sugiyama S. , Doi K. , Takamori H. , Kanemitsu K. , Hirota M. , Baba H.
Published: March 2020

15064

Background: Radio-frequency ablation (RFA) and microwave coagulation therapy (MCT) have been developed as a useful locoregional treatment for hepatocellular carcinoma (HCC). It is still unclear which ablation therapy is superior for the patients with HCC, from the viewpoint of not only short term but also long term outcome. Methods: Between January 1991 and December 2005, 430 patients with HCC were treated with ablation therapy (230 RFA and 200 MCT) in our institution. Enroll criteria of this therapy were as follows; 1) unresectable HCCs, 2) each smaller than 3 cm, 3) up to three nodules, 4) without vascular invasion. Either percutaneous (P), endoscopic (E) or open (O) approach was selected individually based on location, size, number, or other factors. Treatment was repeated until complete ablation of HCC. Results: 1. Proportion of Child B or C was 62% and 60%; Stage III or IV was 56% and 58% in the patients with RFA and MCT, respectively. 2. Average tumor size and tumor number was 27mm/2.5 and 26mm/1.9 in the two groups. 3. Approaches were P: 55%, E: 33%, O: 12% in RFA and P: 48%, E: 30%, O: 22% in MCT. 4. Number of treatment was 1.1 in RFA and 1.2 in MCT. 5. Recurrence rate at the therapeutic site was 8% in RFA and 12% in MCT. Especially, endoscopic RFA provided a quite low recurrence rate (3%). 6. Cumulative 5-year survival was 52% versus 45% in the two groups. 7. Complication rate was significantly lower in RFA (5%) compared to MCT (11%). Intraabdominal tumor seeding (1% in MCT) and liver abscess formation (4% in MCT) was never encountered in RFA. Conclusions: Radio-frequency ablation for hepatocellular carcinoma is a safer procedure and can provide a similar favorable long- term prognosis compared to microwave coagulation therapy.

No significant financial relationships to disclose.
Phase I/II study of combination chemotherapy with S-1 and cisplatin every 3 week schedule in patients with metastatic or recurrent gastric cancer
Authors: Lee J. , Kang H. , Kang Y. , Ryu M. , Chang H. , Kim T. , Sohn H. , Kim H. , Lee J.
Published: March 2020

15066

Background: S-1 plus cisplatin has been reported to be highly active in advanced gastric cancer (AGC). The objectives of this study were to define the maximal-tolerated dose (MTD) of S-1, given for 2 weeks separated by 1 week rest, with a fixed dose of cisplatin, and to determine the activity and safety of this combination regimen at the recommended dose (RD) when used as the first line treatment of AGC. Methods: Cisplatin was fixed at a dose of 60 mg/m2 on D1 and the starting dose of S-1 was 30 mg/m2 bid (level I) on D1 to D14 every 3 weeks. The dose of S-1 was increased by 5 mg/m2 bid up to 50 mg/m2 bid (level V) unless MTD was achieved. At every level, a cohort of 3 patients (pts), which could be expanded to 6 pts, was studied. Dose-limiting toxicities (DLTs) were assessed for the first 2 cycles. Results: From February 2004 to January 2006, 62 eligible pts were enrolled. In phase I (N=21), DLTs occurred at level V (S-1 50 mg/m2 bid), with 2 of 3 pts developing G3 diarrhea or febrile neutropenia. The RD was determined at level IV (45 mg/m2 bid) because only 1 DLT occurred out of 6 pts at this level. After the first 20 pts (series I) were enrolled in phase II, the protocol was amended; the S-1 dose was reduced down to 40 mg/m2 bid (level III, series II, N=23) because of poor bone marrow recovery and resultant treatment delay. At the time of analysis, a total of 272 cycles of chemotherapy were administered. The median age was 52 years (28–70) and ECOG PS was 0/1 in 98% of pts. The objective response was observed in 20(47%; 95% CI, 36–66%) of 43 pts. SD was achieved in 15 (35%) pts. With a median FU of 12.1 months (range 9.8–23.3) for all survivors, median PFS was 5.3 months (95% CI, 4.6–6.0 months) with a median OS of 10.0 months (95% CI, 5.1–14.8 months). G3–4 toxicities included neutropenia (33%), anemia (31%), anorexia (24%), and asthenia (14%); however severe febrile neutropenia, abdominal pain, and stomatitis were never observed. Conclusions: The cisplatin plus S-1 regimen incorporating 2-weeks on and 1-week off is highly active against gastric adenocarcinoma with favorable toxicitiy profiles in Korean patients.

No significant financial relationships to disclose.
Follow up of a multicenter phase II study of sequential paclitaxel and S-1 (TXL/S1) as postoperative adjuvant chemotherapy for gastric cancer (GC)
Authors: Tsuburaya A. , Murata N. , Kimura M. , Ueda Y. , Takahashi M. , Yoshino S. , Takagi M. , Morita S. , Sakamoto J.
Published: March 2020

15084

Background: Of patients who undergo R0 resection for GC with serosal invasion (T3–4), more than half recur mainly in the peritoneum, while TXL and S1 exhibited efficacy for diffuse type and peritoneal metastases in the phase II studies. Primary analysis of the sequential chemotherapy with TXL/S1 had shown its safety and tolerability, its survival benefit is being tested in a large phase III study (the SAMIT trial) with oral fluoropyrimidines as controls. The analysis for survival of this preceding phase II study is performed. Methods: Eligibility criteria included histologically proven GC; sT3–4; sN0–2; M0 (except peritoneal cytology: CY); post D2–3 gastrectomy and R0–1; ECOG PS 0–1; and 20–80 years old. On postoperative day 14 to 56, patients received 3 courses of weekly TXL (80mg/m2 on day 1, 8 for the 1st course and on day 1, 8, 15 for the 2nd and 3rd courses, repeated every 3 or 4 weeks) followed by 4 courses of S1 (80mg/m2 daily for 2 weeks, repeated every 3 weeks). The primary endpoints were % of patients who completed all 7 courses (compliance) to see whether the lower 95% confidence limit of compliance was greater than 69% and incidence of severe toxicities and the secondary endpoints were 3-year survival and toxicities. Results: 50 patients were accrued from May 2003 to March 2004. The median age was 63 (range 34–74); male/female: 34/16; pT2/T3/T4: 1/44/5; CY0/CY1: 4/46; f-stage2/3a/3b/4: 12/15/16/7. The overall compliance was 84%. Median follow up time was 1063 days for survivors (694–1332) and 1030 days for all. Three-year DFS were 64.6% for all, 66.1% for CY0 and 50.0% for CY1. Conclusions: Sequential TXL/S1 may serve as an active adjuvant for gastric cancer patients especially who are at high risk for peritoneal spread.

No significant financial relationships to disclose.
Pilot study of selective internal radiation therapy (SIRT) for patients with unresectable neuroendocrine liver metastases (NETLM)
Authors: King J. , Quinn R. , Glenn D. , Liauw W. , Janssen J. , Morris D.
Published: March 2020

15096

Background: Few effective treatment options exist for inoperable NETLM. A prospective single-unit study assessed safety and efficacy of radioactive yttrium90 resin (SIR) in 34 patients with unresectable (NETLM). Method: Microspheres were administered via temporary percutaneous hepatic artery catheter with concomitant 7day 5-flurouracil infusion. Patients were monitored prospectively and treatment response measured by CT imaging and chromogranin A (CgA). Results: 34 patients (22 male), mean age 61 years (range 32–79) were treated with SIRT from December 2003 to December 2005. Mean follow-up 28.9 months, (95% CI 23.4 to 32.3). Complications were: post-embolitic pain and lethargy 1 week-1 month; 3 radiation gastritis, 2 of whom developed a duodenal ulcer. RECIST response on CT scan of 34 patients at 1 month: PR 9 (26%); SD 22 (65%); PD 3 (9%); 32 at 6 months, PR 7 (22%); SD 19 (59%); PD 6 (19%); 29 at 12 months CR 2 (7%); PR 3 (10%); SD 16 (55%); PD 8 (28%); 16 at 18 months, CR 4(25%); PR 1 (6%); SD 8 (50%); PD =3 (19%); 8 at 24 months, CR 4 (50%);SD 2 (25%),PD 2 (25%); 6 at 30 months, CR 2 (33%); SD 2 (33%); PD 2 (33%). CgA U/L fall from entry was: 19 (26%) at one month; 15 (43%) at 6 months; 15 (52%) at 9 months; 11 (57%) at 12 months; 8 (38%) at 24 months and 4 (80%) at 30 months. At 36 months from entry 11 (32%) have died; 8 (24%) have PD; 9 (26%) have SD and 6 (18%), (15 to 30 months) have CR on CT scan. Conclusion: SIRT is a promising treatment option for patients with in-operable NETLM.

No significant financial relationships to disclose.
Gemcitabine and carboplatin in the treatment of metastatic cholangiocarcinoma and gallbladder cancer
Authors: Suresh R. , Picus J. , Sorscher S. , Fournier C. , Tan B. R.
Published: March 2020

15102

Background: There is currently no standard therapy for patients with unresectable or metastatic biliary tract cancers. Gemcitabine has been shown to be active against these tumors with a 20–30% response in various phase II studies. Gemcitabine is also synergistic with platinum compounds. Aim: We conducted a Phase II study of gemcitabine plus carboplatin in patients with unresectable or metastatic choloangiocarcinoma or gallbladder cancer to assess the regimen’s safety and efficacy. Methods: Since 3/2002, 49 (48 evaluable) patients were treated with gemcitabine at 1000 mg/m2 IV over 30 minutes days 1 and 8 with carboplatin at AUC 5 IV on day 1 of a 21 day cycle. There were 34 women and 15 men enrolled. Ages ranged from 34 to 87 with a median age of 65 years. Results: Best radiologic responses - 5CR, 9 PR, 24 stable disease and 10 progression. CR+PR 14/48 (29.2%) and stable disease 24/48 (50%). Toxicity: Hematological toxicities: Grade 3 neutropenia 33%, febrile neutropenia 0.02%, anemia 12.5% and thrombocytopenia 14.6%. Grade 4 hematological toxicites were rare - neutropenia 0.04%, and thrombocytopenia 0.06%. Non-hematologic toxicities were generally mild (fatigue, edema, nausea, vomiting, elevated liver enzymes, electrolyte abnormalities). Except for one patient who had depression there were no grade 4 non-hematological toxicity. Grade 3 non- hematological toxicites were also rare occurring only in 1 to 3 patients. Conclusions: Gemcitabine and carboplatin is active against biliary cancer and is highly tolerable. This study is being supported by Eli Lilly & Co.

No significant financial relationships to disclose.
Differential response of factor VIII and protein C expression following multimodal therapy for esophageal carcinoma
Authors: Byrne M. , M B. , O’ Donnell J. , White B. , Kennedy J. , Reynolds J.
Published: March 2020

15106

Background: Tumour growth is associated with development of a hypercoaguable state and increased risk of thrombosis. Factor VIII plasma concentration has been shown to be an independent and dose-dependant risk factor for venous thromboembolism. Von Willebrand factor, the carrier molecule of circulating FVIII is expressed by vascular endothelial cells and in vitro observations indicate that chemotherapy induces endothelial damage with subsequent dysfunction. This study assessed FVIII, Protein C and Protein S response following multi modal therapy for oesophageal carcinoma. Methods: Fifty oesophageal cancer patients were studied, (multimodal n= 25, surgery only, n=25), at time points 0 (pre-operatively, following the first and final cycles of chemoradiation, and on days 1, 3, 7, 14, 21 and 28 days, and at 3 and 6 months postoperatively. Blood samples were collected and centrifuged at 3000g for 20 minutes to botain platelet poor plasmad. Factor VIII levels were measured by one stage clotting assay with factor VIII-deficient plasma. Automated functional assays for Protein C and Protein S in plasma were performed. Results: Factor FVIII levels were significantly elevated in the multimodal cohort following the 1st (p<0.008) and 2nd (p<0.001) cycles of chemoradiotherapy and at all time points following surgery, compared to baseline readings (p<0.001). Similar elevation was noted in the surgery only patients. No significant difference in factor FVIII levels between the multimodal group and surgery only patients was seen, except on day 21 (p < 0.04). Preliminary findings indicate a significant difference between the multimodal and surgery only cohorts in Protein C (0.74–1.32 IU/ml) levels (p < 0.05) at two timepoints. Conclusion: Factor VIII serum levels are significantly elevated following preoperative chemoradiotherapy. The pattern of response post oesophagectomy did not differ between the two cohorts. Elevated levels are a risk factor for both primary and recurrent venous thrombolism. The precise pathogenetic mechanism and cause of this elevation remains to be elucidated. Further studies investigating Protein C activity and, relating Factor VIII to thrombosis and inflammation in the oesophageal cancer patient are required.

No significant financial relationships to disclose.
The utility of HCC screening among cirrhotics
Authors: Niravath P. , Hayes T. , Hilsenbeck S.
Published: March 2020

15108

Background: Screening known cirrhotics for hepatocellular cancer (HCC) has long been a contentious topic. Studies to date have failed to conclusively prove or disprove the validity of AFP and hepatic ultrasound as screening mechanisms for HCC among cirrhotics, particularly in the American population. It is not clear whether these screening mechanisms provide any benefit in terms of reduced morbidity and mortality. Methods: The study examined all cirrhotics who developed HCC at the Houston Veterans Affairs Medical Center between 1999 and 2005. Those who were screened with AFP and/or imaging (either ultrasound, triphasic liver protocol CT, or MRI) were compared to those patients who were not screened at all. The screened and unscreened patients were compared in terms of Barcelona Clinic Liver Cancer Stage (BCLC) at the time of diagnosis. Results: Statistical analysis revealed a significant difference between the screened and unscreened groups in terms of BCLC stage at diagnosis, with the unscreened group being diagnosed at later stages than the screened group. Of the 155 patients observed, 26 were appropriately screened, and 129 were not. The BCLC stages at diagnosis for the two groups are shown in the table . The different trend in the two groups was found to be statistically significant with a p-value of 0.004. Furthermore, among the screened group, no particular method of screening (AFP vs. imaging vs. combination) was shown to be superior to another. Conclusions: Screening for HCC among cirrhotics using AFP and/or imaging every 6 months does correlate with HCC diagnosis at an earlier BCLC stage, thus portending better treatment options and improved prognosis. Therefore, screening all known cirrhotics for HCC may lead to decreased mortality.

[Table: see text]

No significant financial relationships to disclose.
Patterns of care and outcome of patients with gastroenteropancreatic neuroendocrine tumors (GNETs): Results from a Spanish multi-center hospital-based tumor registry
Authors: Garcia-Carbonero R. , Vilar E. , Alonso V. , Martínez del Prado M. , Sevilla I. , Crespo G. , Teulé A. , Llanos M. , Castellano D. , Salazar R. ,   Spanish Group of Neuroendocrine Tumors (GETNE)
Published: March 2020

15110

Background: GNET represent an unusual family of neoplasms with a wide and complex spectrum of clinical behavior. To provide information regarding demographic characteristics, diagnostic procedures, tumor features, therapeutic interventions and outcomes of pts with GNETs, a national tumor registry was launched. We present here the results of this broad-based multi-institutional observational registry that comprises 41 sites representing all regions of Spain. Methods: Data was provided at www.retegep.net by participating centers and assessed for internal consistency by external independent reviewers. Results: The study cohort comprised 474 pts (57% male, median age: 59 years). 52% were carcinoids (C), 18% non-functioning pancreatic tumors (PT), 9% insulinomas and 6% gastrinomas. Most common primary tumor sites included midgut (19%), and head (14%) and body of the pancreas (9%). 10% were of unknown primary. Functioning symptoms led to diagnosis in 29% of cases. 5% were associated to MEN1. Diagnostic workup included serum hormone tests (60%), ultrasound (40%), CT scan (75%) and octreoscan (37%). 32% of pts presented with localized tumors (L), 14% with local-regional spread (LR) and 44% with advanced disease (Adv). Treatment for Adv disease consisted of somatostatin analogues (SA) (48%), surgery (45%), chemotherapy (CT) (42%), interferon (IFN) (23%), chemoembolization (9%) and radiofrequency ablation (5%). 5-year survival (5yS) for the whole group was 61.1% (SD:3.4%), 78.2% (SD:5.4%) for pts with L/LR disease and 47.1% (SD:5.6%) for Adv stages. 5yS rates were similar for C and PT tumors, also when stratifying according to tumor stage (84 and 76% for local-regional disease, and 51 and 49% for Adv disease). 1st line systemic therapy (n=175) consisted of CT (42%), SA (39%), IFN (5%), SA+IFN (10%) and SA+CT (3%), with 5yS rates of 59%, 36%, 42%, 46% and 38%, respectively (p=0.7). As second line systemic treatment (n=65) 45% received CT, 26% SA, 15% immunotherapy and 14% different drug combinations. Conclusions: This national database reveals relevant information regarding current Spanish practices and will provide valuable insights into the epidemiology and management of this heterogeneous uncommon disease

No significant financial relationships to disclose.
Response to trans-arterial chemoembolization prior to orthotopic liver transplantation or hepatic resection in patients with hepatocellular carcinoma
Authors: Almhanna K. , Golshayan A. , Sands M. , Levitin A. , Kim R. , Pelley R. , Kalmadi S.
Published: March 2020

15114

Background: Trans-arterial chemoembolization (TACE) is often used as pre-operative therapy for patients with hepatocellular carcinoma (HCC) prior to orthotopic liver transplantation (OLT) or hepatic resection (HR). However, the benefit of response to TACE on overall survival (OS) and progression free survival (PFS) remains unclear. Methods: Complete data was available for 24 patients with HCC who underwent TACE prior to either OLT or HR from 1998–2006. Known prognostic factors including tumor size, histology, number of nodules, Child-Pugh class, Okuda stage, MELD score, CLIP score were recorded. Clinical features before and after TACE were identified and tested by univariate analysis. Results: The mean patient age was age 51 years (range 31–65). Underlying diagnoses included: HBV (17%), HCV (54%), alcohol abuse (63%), cryptogenic (8%), nonalcoholic steotohepatitis (4%). The mean maximum tumor diameter was 6.2 cm (range 1.6–16.1 cm), with 13 tumors (54%) measuring >5 cm. The median number of lesions were 2 (range 1 - 7). The Milan criteria was met in 15 patients (63%). Eighteen subjects underwent OLT, while 6 had HR. Median PFS was 35 months (m) (95% C.I. 17–58 m). One- and three-year OS were 95.8% and 73%, respectively. TACE was performed within a mean time of 2.5 months from diagnosis (range 0.5–9 m). Post-TACE, eleven subjects demonstrated a biologic response, defined as decrease in serum alfa-fetoprotein (AFP) by >50%, or reduction in AFP level to <10 ng/mL. However, biologic response did not predict for improved PFS (p =0.41). Additionally, nine patients had a radiographic response to TACE as measured by RECIST criteria, but this also did not predict for improved PFS (p = 0.79). Only tumor size >5 cm (p = 0.04) and CLIP score (p = 0.01) were found to be independent predictors of improved PFS. Conclusions: Neither radiographic nor biologic responses to TACE appear to serve as selection criteria for OLT or HR. Those patients who fail to demonstrate response to TACE should not necessarily be denied surgical therapy. Larger, prospective trials are needed to better evaluate which patients will benefit most from TACE prior to OLT or HR.

No significant financial relationships to disclose.
Maltodextrin supplemented diet prevents postoperative weight loss during the first months after gastrectomy for gastric cancer
Authors: Raida M. , Mestrom H. , Delbrück H.
Published: March 2020

15127

Background: Postoperative nutritional status is a major factor determining the outcome after gastrectomy for gastric cancer. However, weight loss is a regular consequence after gastrectomy for gastric cancer. This weight reduction occurs during the first months, after which the weight curve seems to stabilize. Aim of this study was to determine the effect of maltodextrin supplemented diet on postgastrectomy weight loss. Methods: In 2005 we introduced a liquid supplementation of maltodextrin to the conventional solid dietary schedule of patients who had underwent gastrectomy for gastric cancer. Between 01/2005 and 6/2006 87 consecutive patients with gastric cancer were included in the study. They were admitted to our hospital for a 3–4 weeks period of oncological rehabilitation, median age was 70 years, gastrectomy had been carried out up to 8 months before study inclusion. Oral nutrition followed the recommended dietary guidelines to avoid postgastrectomy dumping syndrome. This diet was supplemented with 150 g of maltodextrin, dissolved in 1 litre of tea (600 kcal). Weight changes in this study population were compared to a control population of 65 consecutive patients with gastric cancer who had been admitted to our hospital between 01/1992 and 12/1993, matching the same inclusion criteria as the study population but fed without the supplementation of maltrodextrin. Results: During the 3–4 weeks rehabilitation period patients from the maltodextrin study group were able to reach an average weight gain of 407g while patients from the control group lost in average 352 g during the same time span. We observed that weight gain substantially improved the psychological condition of the patients. Postgastrectomy dumping syndrome was similar in both groups depending on strict control of the dietary schedule. Conclusions: We conclude that a maltodextrin supplemented diet can effectively prevent postoperative weight loss during the first months after gastrectomy for gastric cancer.

No significant financial relationships to disclose.
The hormone replacement therapy opposed to low dose tamoxifen (HOT) study: safety data from an ongoing phase III trial
Authors: Bonanni B. , Santillo B. , Serrano D. , Rotmensz N. , Muraca M. , Vella A. , Belloni C. , Ponti A. , Veronesi U. , Decensi A.
Published: March 2020

1514

Background: Primary prevention trials have shown that tamoxifen (T) lowers ER+ breast cancer (BC) incidence by 48%. While the IBIS I update showed mixed findings, the Italian trial showed an interesting positive risk/benefit ratio in T and hormone replacement therapy (HRT) users: fewer BC, endometrial cancer comparable to placebo, and no cardiovascular diseases (CVD) excess. In a phase II study, low dose T and HRT showed a safe gynecological profile and did not increase menopausal symptoms. Moreover low dose T maintains the same antiproliferative effects as the standard dose. To improve BC prevention and quality of life (QoL) in menopausal women we started a multicentric, phase III trial of low dose T in HRT users. Methods: current or de novo HRT users are randomized to T 5 mg/day or placebo for 5 yrs. The primary aim is the reduction of invasive or in situ BC. Secondary aims are: safety, gene polymorphisms (SNPs) correlated to BC risk and T activity. In a subgroup transvaginal ultrasound (TvUS) and endometrial biopsy is being performed after 3 years of treatment to monitor endometrial effects. Results: as of December 31 2006, 1870 women were enrolled, of which 21% were hysterectomized. Median age is 53 years (33–72), BMI is <25 in 66%, =25<30 in 26%, >30 in 8%. Current or de novo users are 80% and 20%. 84% participants have at least one follow-up visit. 128 subjects performed already the 3 years TvUS and endometrial biopsy: so far no atypical hyperplasia or cancer was found. A modest increase of menopausal symptoms was observed (hot flashes 42% vs 52%, night sweating 39% vs 44%). Drop-outs are 23%, of which 13% due to AE including: 21 cancers (12 invasive BC, 1 DCIS), 13 CVD (3 VTE), 9 gynecological (5 endometrial polyps). Conclusions: combination of low dose T and HRT has reasonable safety profile, we have reached almost 1,900 women on study and AE rate is very low. These unblinded findings support the safety of the association of HRT and T.

No significant financial relationships to disclose.
Chemotherapy in gallbladder cancer: Improving survival
Authors: Gallardo J. , Rubio B. , Ahumada M. , Villanueva L. , Barajas O.
Published: March 2020

15140

Background: Since 1999 we had been studying the effect of chemotherapy in gallbladder cancer, a disease frequent in low economical income area of the world, orphan of research, traditionally considered chemotherapy-resistant. Previous studies included 5- FU regimen and communicated response rate of 10–26 %, and no changes on survival. We first conducted a phase II study with gemcitabine (Gem), and later, another study (with support of GOCCHI) using Gem and cisplatin (C). Since 2001 we had treated patients out of clinical trial. We compare median survival observed in all series. Methods: Patients file of both 2 phase II studies and clinical record of all patients treated out of clinical trial were retrieved and median survival was calculated. The both phase two trials had a similar population, and inclusion criteria, both were multicenters. The third cohort is a one center experience. The regimens used were: Gem 1,000 mg/m2 on days 1,8 and 15 every 28 days (first trial), Gem 1,250 mg/m2+C 35 mg/m2 on the 1 and 8 days every 21 days (second trial), only maximum 6 courses were planned. The third group, most frequently, received Gem 1.000 mg/m2 (10mg/m2/min)+C 40 mg/m2 days 1 and 8 every 21 days, until disease progression and/or toxicity; second line chemotherapy was allowed. Among whole group 7 pts, who had significant response, underwent a surgical resection. Survival was also calculated and comparison is included. The toxicity was evaluated every 2 weeks and response was assessed every two cycles using CT scan. Overall survival was calculated from beginning of chemotherapy until death or last follow up. Survival analysis was also done using Kaplan Meier’s tables Results: For Gem monotherapy (26 pts) median survival was 30 weeks, for Gem+C (44 pts) median survival was 28 weeks. For third group (29 pts) median survival was 56 weeks. Until now, for the 7 pts who underwent a surgical resection median survival is 92 weeks, with one pt alive, without evidence of disease, at 112 weeks of follow up Conclusions: Both regimens showed better efficacy than 5-FU based chemotherapy, the combination did not show better survival. The third group has better median survival, probable due to the use of second line therapies. Combining chemotherapy + surgical resection may be a better treatment for some few, well selected patients.

No significant financial relationships to disclose.
Taxane based neoadjuvant chemotherapy in locally advanced esophageal cancer: A single centre experience
Authors: Ambulkar I. B.
Published: March 2020

15143

Background: Neoadjuvant taxane based chemotherapy may improve response rate in patients with locally advanced esophageal cancer. We have evaluated paclitaxel based induction chemotherapy in patients with locally advanced esophageal cancer to determine its feasibility, clinical response, radiological and endoscopic response. Methods: etween November 2004 to October 2006, 30 patients were enrolled in this study. All patients were categorized as locally advanced esophageal cancer. They underwent CT scan chest and upper GI endoscopy before chemotherapy and 3 cycles after the chemotherapy. Chemotherapy included 3 cycles of paclitaxel (135 mg/m2 on day 1),5FU (500 mg/m2 on day 1,2,3) and cisplatin (25 mg/m2 on day 1,2,3) every 21 days. The main endpoint was response evaluation. Twenty one (70%) had squamous cell carcinoma and 9(30%) had adenocarcinoma. Median age was 44 years (39–75), 22(73.3%) were males and 8 were(26.6%) females. Dysphagia was the predominant symptom in 28 (93.3%) patients. Results: All 30 patients were evaluable for response and toxicity. Radiological and endoscopic CR was seen in 6(20%), PR in 16(53.3%),5(16.6%) had SD and 3(10%) had PD. Twenty five (83.3%) patients underwent radiotherapy to a total dose of 4500 cGY,5(16.6%) underwent surgery, 2(6.6%) showed complete pathological response. Observed toxicity was predominantly hematologic and leucopenia grade III/IV in 10% of cycles, Hb grade III/IV in 6.6% and thrombocytopenia grade III/IV in 3% of cycles.6.6% patients developed grade III/IV oral mucositis. Conclusions: Addition of paclitaxel to cisplatin and 5FU as neoadjuvant chemotherapy in esophageal cancer appears to be highly effective with complete as well as partial response rates. It can be given safely with manageable side effects. It is predicted that combination of paclitaxel, cisplatin and 5FU having excellent response as neoadjuvant therapy will also produce long term benefits.

No significant financial relationships to disclose.
Clinical outcome prediction in esophageal adenocarcinoma based on tumor and germ-line single nucleotide polymorphisms (SNP) in DNA-repair pathways
Authors: Yoon H. , Murphy K. M. , Gibson M. K.
Published: March 2020

15144

Background: Germ-line SNPs in DNA repair enzymes are studied as predictive factors in various cancers. More rarely studied, however, is the presence of SNPs in tumor cells and how they relate to both germ-line SNPs as well as outcome. We explored the presence of and relationship between germ-line and tumor SNPs in esophageal adenocarcinoma using two systems: (1) Cell lines, to determine whether loss of heterozygosity (LOH) occurs near DNA repair genes, and for genotyping; (2) Patient samples, to determine whether SNPs differ between normal and tumor mucosa. Methods: (1) For LOH analysis, we examined three short tandem repeat (STR) loci on 19q13.2- 13.3 (near DNA-repair genes XPD, ERCC1, and XRCC1) in four esophageal adenocarcinoma cell lines. (The STR markers have a false positive rate of <10-3 for LOH when all three demonstrate homozygosity.) Then, using a real-time PCR allelic discrimination TaqMan assay (AB), we analyzed two SNPs of interest in these cell lines. (2) We performed SNP analysis on tumor and adjacent normal mucosa from paraffin-embedded esophageal specimens taken at resection in patients with T3N0–1 esophageal adenocarcinoma who received preoperative cisplatin, paclitaxel, gefitinib and radiotherapy followed by transhiatal resection. Results: (1) Cell lines: SEG1 and BiC1 were consistent with LOH, showing a single-allele pattern at XPD 751 (C allele) and XPD 312 (G allele). TE7 and SKGT4 did not have LOH. (2) Tumor and normal tissue: We obtained data on two patients for XPD 751. Genotypes in normal mucosa were heterozygous for one patient and homozygous at the minor allele (Q/Q) for the second patient. Genotypes in tumor were identical to those in normal tissue. Conclusions: Our cell line data shows that LOH occurs in esophageal tumor cells at DNA-repair genes of interest. Our data in two patients with esophageal adenocarcinoma did not demonstrate a difference at XPD 751 between tumor and normal tissue. Given the technical success and encouraging data from this work, we plan to evaluate tissue from ∼90 patients who underwent preoperative cisplatin-based chemoradiotherapy followed by surgery (as part of completed ECOG trial E1201).

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