bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docetaxel (Do) and gemcitabine (Gem) in advanced pancreatic cancer (APC) patients (pts): A multicentre study
Authors: Des Guetz G. , Chauvenet L. , Paraiso D. , Mayeur D. , Aparicio T. , Chirat E. , Boiron C. , Bouleuc-Parrot C. , Pujade- Lauraine E. 
Published: March 2020

15065 Background: Gem is the only approved chemotherapeutic drug in the treatment of APC. Do as single agent has shown some activity. Effective cytotoxic combinations with gem are urgently needed. Methods: Combination of Gem 1200 mg/m2/d1 + Do 50 mg/m2/d1 every 2 weeks was evaluated in first line APC pts with Karnovsky Index (KI) > 40, and good organ function. Initial Do dose was modified according to liver biology alterations. Treatment of relapse with Gem-Do or other combinations was allowed. Results: The 45 pts (male=64%) included in 7 centres had a median age of 62 yrs (range 36–81 yrs) and 26 (58%) had metastatic disease. Pts received a median of 4 cycles (0–6) with a median dose of 47 mg/m2 for Do and 1170 mg/m2 for Gem. Neutropenia Gr 3/4 was the most severe toxicity (Tox) (24% of pts) and required G-CSF support, with infection G3 in 14 pts (31%), febrile neutropenia in 1. Others G3 Tox were fatigue (20% of pts), diarrhea (14%), anemia (9%) thrombopenia (7%) and G2 Tox: alopecia (33%), nausea (15%) and edema (11%). During treatment, KI improved or was stable in 33% and 44% of pts, weight increased or was stable in 38% and 23%, pain control was better or stable in 20% and 56%. After panel review, objective RECIST response was observed in 17.7% of pts (CR = 4.4%) and stable disease in 40%. Median progression- free survival (PFS) was 3.8 months (mo) and 14 pts (31%) had PFS between 6 and 14 mo. Median survival was 12.0 mo (95% CI; 10.2–13.8 mo). Conclusions: The combination of Do and Gem every 2 weeks is feasible and should be associated with systematic growth factor support. Subjective and objective criteria of efficacy in APC are encouraging. A direct comparison with Gem single agent is warranted. No significant financial relationships to disclose.
Dose-dense chemotherapy (CT) with modified TCF regimen (TCF-DD) in metastatic gastric cancer (MGC): A Phase II study
Authors: Dalla Chiesa M. , Tomasello G. , Buti S. , Negri F. , Buononato M. , Longarini R. , Porzio R. , Lazzarelli S. , Brighenti M. , Passalacqua R. 
Published: March 2020

15068 Background: Previous studies reported that in lymphomas, early breast and bladder cancer, dose-dense CT is more effective than conventional treatment. We reported for the first time, in 2006 ASCO meeting, the feasibility of an intensified dose-dense TCF regimen (q2w) in MGC. This is the subsequent phase II study. Methods: patients (pts) with histologically confirmed measurable MGC, ECOG PS 0–3, received up to 6 cycles of Docetaxel 85 mg/m2 (75 mg/m2 after first 12 pts, 70 mg/m2 after the 28th patient) day 1, Cisplatin 75 mg/m2 day 1 (60 mg/m2 after the 28th patient) l-Folinic Acid 100 mg/m2 day 1 and 2, followed by 5-Fluorouracil 400 mg/m2 bolus day 1 and 2, and then 600 mg/m2 as a 22 hour continuous infusion day 1 and 2, every 14 days, plus Pegfilgrastim 6 mg on day 3. Pts with a PS > 1 and/or age > 65 years and/or pre-treated for the metastatic disease, received the same schedule with a dose reduction by 30%. Results: 31 consecutive pts were enrolled (81% male, 19% female; median age: 60, range 40–79; median ECOG PS: 1, range 0–3; 3 pts pre-treated). Primary end points were response rate and safety. A median of 4 cycles (range 1–6) per pts were administered. 15 pts (48%) required a dose reduction, mostly because of hematologic toxicity and severe asthenia. 10 pts (32%) were treated with full dose without any delay on at least the first 4 cycles. 25 pts were evaluated for response (3 too early, 1 early suspension because of severe allergic reaction to Docetaxel; 2 early deaths: 1 bowel perforation and 1 sepsis) and 30 for toxicity. 2 CR (multiple liver metastases), 12 PR, 4 SD and 7 PD were observed, for an ORR (RECIST criteria and intention-to-treat principle) of 50% (95% CI 30–65). At a median follow-up of 10 months (range 1–24), overall median survival was 6 months (range 1–20). Frequent grade 3 to 4 toxicities were: neutropenia (65%), thrombocytopenia (31%), anemia (14%) febrile neutropenia (31%), asthenia (62%), diarrhoea (21%) and stomatitis (14%). Conclusions: TCF-DD regimen in MGC is feasible and very active. The recommended dose (with reduction by 30% as above) for further randomised studies comparing TCF-DD with standard TCF is Cisplatin 60 mg/m2 and Docetaxel 70 mg/m2. No significant financial relationships to disclose.
Daily dose of perifosine less toxic than weekly and active in patients with hepatocellular carcinoma (HCC)
Authors: Campos L. T. , Stephenson J. , Swan F. , Richards D. , Birch R. , Henderson I. 
Published: March 2020

15072 Background: P is a novel oral alkylphosphocholine with effects on multiple signal transduction pathways including Akt, MAPK and JNK. Unresectable HCC has a dismal prognosis. In the only large randomized trial, the response rate to single agent chemotherapy was <3% and median progression free survival (PFS) was l0 weeks. In small series response rates up to 25% have been reported with combination regimens Methods: Patients (pts) were accrued to a broad phase 2 trial & randomized to P, 50 mg daily or 1200 mg weekly, between 3/05 and 5/06, at which time the protocol was amended to P 100 mg daily or 900 mg weekly because the daily dose was so non-toxic and the weekly dose too toxic. The amended protocol is still open. A Simon two-stage design was used for each cancer, and HCC is one of several tumor types that have fulfilled criteria for expansion into the second stage. Results: Prior to protocol amendment 241 pts, including 13 with HCC, were entered. The daily dose was very well tolerated; 70% had no or only grade 1 toxicity. The principle toxicities are gastrointestinal and fatigue. (See table ) The weekly dose was significantly more toxic. The median age of the HCC pts was 64(range 22 - 80); 9 patients were male and the median ECOG performance status was 1, range 0–2. Eight had no prior chemotherapy. Eleven were evaluable for response, and 1 without prior chemotherapy who was treated on the 50 mg daily dose had a partial response lasting for 9 months. In addition, 5 (4 on the 50 mg daily dose) were progression free for > 6 months. This included 2 with 2 and 3 prior regimens. Conclusions: This study demonstrated that perifosine has very little toxicity when administered at a dose of 50 mg daily and is active in HCC as well as other cancers [Table: see text] No significant financial relationships to disclose.
Hemangiogenic response after pre-operative COX2 inhibition predicts recurrence in esophageal cancer
Authors: Jin D. , Port J. L. , Lee P. , Zhang L. , Ferrara C. A. , McDonald K. A. , Meherally D. , Rafii S. , Altorki N. K. 
Published: March 2020

15077 Background: Growth of esophageal cancer involves a proliferative hemangiogenic component. Biomarkers that predict this propensity in esophageal cancer and the impact of anti-angiogenic strategy on their levels as well as clinical response remain unknown. Methods: A multimodular approach was devised to assess hemangiogenic parameters in a cohort of chemotherapy naïve patients with locally advanced (T2-T3N0, T1-T3N1M0M1a) esophageal cancer pre- and 4 days post-celecoxib neoadjuvant treatment. Patients went on to receive neoadjuvant therapy with celecoxib, paclitaxel and carboplatin for 3 cycles, followed by surgical resection. This bioassay panel consists of 5 components: i) HUVEC-based angiogenic scale for functional plasma angiogenic activity, ii) flow cytometry to quantify CD133+VEGFR2+ circulating endothelial progenitors (CEPs), iii) hematopoietic colony-forming assay to quantify circulating hematopoietic progenitors (CHPs), iv) plasma SDF-1 level, and v) platelet VEGF-A level. Results: The cohort consists of 8 consecutive patients (6 men, 2 women) with median age of 58. After 18 months of followup, 6 patients remained alive and without evidence of recurrence, while 2 had tumor recurrence and metastasis. Analysis of the positive responders (pre-celecoxib baseline versus 4 days post treatment) revealed a global suppression of hemangiogenic parameters with reduction of the functional HUVEC-based angiogenic scale (mean score of 3.3 versus 1.8; p<0.05), 2.2-fold decrease in CEPs (p<0.05), and 3-fold decrease in CHPs (p<0.05). This trend also correlated with decreased plasma SDF-1 and platelet VEGF-A levels . However, in the 2 cases of tumor recurrence, the initial hemangiogenic response was blunted with no significant difference in all parameters tested during the celecoxib monotherapy period. Conclusion: Esophageal cancer development involved a hemangiogenic switch toward increased CEPs, CHPs, and functional plasma pro-angiogenic activity. COX2 inhibition with celecoxib normalized the hemangiogenic profile. Collective assessment of hemangiogenic biomarkers during neoadjuvant setting may be a promising tool in predicting clinical outcomes, recurrence, and for validating impact of anti-angiogenic therapy on esophageal cancer. No significant financial relationships to disclose.
Neoadjuvant chemotherapy (CT) and postoperative chemoradiation (PCRT) in locally advanced, resectable, gastric cancer (LAGC). Preliminary results of a pilot study
Authors: Buonadonna A. , De Paoli A. , Sigon R. , Cannizzaro R. , Canzonieri V. , Boz G. , Innocente R. , Rossi C. , De Marchi F. , Frustaci S. 
Published: March 2020

15078 Background: Curative surgery is achieved in fewer than 50% of patients (pts) in LAGC. PCRT has shown significant improvement in disease control and survival but a limited impact on metastatic disease. To improve this results, a combined modality approach, including IORT, was planned. Methods: Pts with resectable LAGC (stage T3–4 and/or N+) were eligible. EGDS, EUS, abdomen CT were used for staging. 3 cycles of ECF (Epirubicin 50mg/mq, q 3wks; Cisplatin 60mg/mq, q 3wks and 21-day c.i. 5-FU 200mg/mq/day) were planned before radical surgery. IORT (10–15 Gy) included the high risk area defined at surgery. Postop RT included gastric area, anastomosis, duodenal stump and draining lymph node stations. RT (41.4–45 Gy in 23–25 fractions) and concurrent c.i. 5-FU (200 mg/mq/day) were administered. An oral caloric intake >= 1500 Kcal was provided. Results: From June 2001 to December 2006, 22 pts (13 M and 9 F), median age 64 yrs (41–74), with uT3N1 (21pts) and uT2N1 (1pt), entered the study. Tumor location was proximal in 10, lower in 8 and middle in 4 pts, respectively. All pts underwent the planned neoadjuvant ECF with a median of 3 cycles (range 3–5). Toxicity was moderate (<= grade 3) without toxic deaths: nausea and vomiting in 3%, mucositis in 3%, hematological in 7%. Twenty/22 pts underwent surgery (in progress in 2 pts) and 15 (75%) had R0 resection. Tumor downstaging was reported in 9/20 (45%) pts (8 pT2, 1pT1). IORT with 12.5 Gy (10–15 Gy) was given to 12 pts and 12 pts had PCRT. Eight pts were excluded from PCRT for postop complications (2 pts), disease progression (3 pts) or pN3 (3 pts). All 12 pts completed RT with a median dose of 41.4 Gy (41.4–56Gy), but 3 (25%) required RT interruption and 5 pts (40%) also definitive 5-FU interruption (overall PCRT compliance of 60%). Major toxicity from PCRT consisted of G3 asthenia and anorexia, requiring parenteral nutrition. Conclusions: Neoadjuvant CT confirmed feasible in LAGC and resulted in a substantial downstaging with a favourable R0 resection rate. Combined modality approach with IORT and PCRT appears attractive, but limited compliance to PCRT was observed. A definitive evaluation and data on disease control and survival will be reported. No significant financial relationships to disclose.
Female sex and standardized mitomycin-c dose are associated with increased risk of neutropenia after hyperthermic intraperitoneal chemotherapy
Authors: Lambert L. A. , Armstrong T. S. , Lee J. J. , Katz M. H. , Eng C. , Wolff R. A. , Ng C. S. , Smith M. L. , Gonzalez-Moreno S. , Mansfield P. F. 
Published: March 2020

15091 Background: Cytoreductive sugery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are being increasingly employed in the managment of peritoneal-based malignancies. Depending on the treatment regimen, neutropenia (NP) is a common and potentially life-threatening early postoperative complication of HIPEC. However, little is known about the incidence or risk factors associated with HIPEC-induced NP. Methods: From January 1993 to October 2006, 120 CRS and HIPEC with mitomycin-c (MMC) were performed in 117 patients with appendiceal neoplasm. NP was defined as an absolute neutrophil count of < 1,000/mm3. Variables assessed as potential risk factors for HIPEC-induced NP included: age, sex, weight, BMI, BSA, splenectomy, dose of MMC (standardized for BSA and nonstandardized), percent of perfusate recovered, length of surgery, estimated blood loss, perioperative blood transfusion, and history of prior chemotherapy. Results: Total perfusate MMC doses ranged between 37.25 and 65 mg. The overall incidence of NP was 39.2%. The NP rates in female and male were 57.6% and 21.3%, respectively. Female sex, BMI, BSA, and the standardized dose of MMC were significantly associated with an increased risk of NP by univariable logistic regression. Female sex and standardized dose of MMC remained statistically significant for an increased risk of NP on multivariable logistic regression. The odds ratio (OR) of NP for females was 3.63 (95% CI: 1.54, 8.52); the OR of NP for a 1 mg/m2 increase in standardized MMC dose was 1.26 (95% CI: 1.11, 1.44). No other variables were identified as independent predictors of increased or decreased risk of NP. Compared to patients without NP, patients with NP had a higher rate of urinary tract infection (42.6% vs. 21.1%, p=0.01) and slightly higher length of stay (median: 24.0 days vs. 18.5 days, p=0.16). Conclusions: NP is a common complication after HIPEC with MMC . Female patients are at significantly increased risk for this complication. Risk of NP also increases with MMC dose standardized for BSA. With increasing interest in the use of CRS and HIPEC, understanding the risk factors for HIPEC-induced NP may facilitate reducing the morbidity associated with this procedure. No significant financial relationships to disclose.
High complete response (CR) rate in patients (pts) with esophageal carcinoma (EC) undergoing neoadjuvant combination of docetaxel and cisplatin (DC) ± cetuximab(DCE) chemoradiation therapy—a retrospective analysis
Authors: Fillos T. J. , Hentschel P. , Watkins K. , Karpeh M. S. , Meek A. , Kim B. , Franceschi D. , Zee S. , Madajewicz S. 
Published: March 2020

15093 Background: EC is a highly lethal disease with 5 year survival less than 15%. Surgery offers a chance for cure in early disease. Still, fewer than 20% of pts treated with surgery alone are alive at 5 years. Neoadjuvant chemoradiation offers the theoretical advantage of increasing R0 resections and reducing early local and distal metastases which may translate into improved survival. Several clinical trials have resulted in pathologic complete response (pCR) rates of 20–30%. Methods: Newly diagnosed pts with EC Stage 2A (T3) to 4 received weekly Docetaxel (D)25–30mg/m2 and Cisplatin (C)25–30mg/m2.for 6–8 weeks concurrently with radiation, 5040 cGy in 28 fractions. Cetuximab (E) 200mg/m2 was added after it became accepted treatment in head and neck cancers. Pts were scheduled 4 - 6 weeks later for surgery followed by the same chemotherapy for total of 16 weeks of treatment. Pts were assessed for time to progression, overall survival and toxicities. Results: Fifteen pts treated in 2005–6 underwent IRB approved evaluation; 11 male and 4 female, median age of 62(range 44–78) . Four had squamous cell (SCC) and 11 adenocarcinomas. Nine pts had Stage II, 4 pts stage III and 2 pts stage IV disease. Seven pts underwent surgery, all R0 resections. Four of them had pCR, one pPR (downstaged from T3 to T1) and two pts had stable disease. An additional 3 pts had radiological and endoscopic proven CR (medically not surgical candidates) for an objective response (CR+PR) in 8 out of 15 pts (3 SCC and 5 adenoca). Five out of 9 receiving DC had an objective response while 3 of 6 receiving DCE responded. Five pts progressed prior to surgery. Grade 3/4 neutropenia occurred in 2, nausea in 3, and 1 pt experienced Grade 3 dehydration. Four patients required dose reductions by 20%. Six patients had one cycle and 2 had 3 cycles delayed by one week each. Conclusions: Neoadjuvant chemoradiation treatment with weekly Docetaxel and Cisplatin ± Cetuximab is tolerable with high rate of CRs. There was no observed difference in response with the addition of cetuximab. A Phase III study is suggested. No significant financial relationships to disclose.
Neoadjuvant gemcitabine/cisplatin for resectable adenocarcinoma of the pancreatic head—a prospective phase I trial
Authors: Heinrich S. , Pestalozzi B. , Schafer M. , Hany T. , Bauerfeind P. , Perren A. , Knuth A. , Clavien P. 
Published: March 2020

15095 Background: Pancreatoduodenectomy (PD) alone was considered a standard treatment for cancer of the pancreatic head for a long time before the recent advent of adjuvant chemotherapy (CTX). Since adjuvant chemotherapy cannot be applied to all patients (pts), and neoadjuvant chemoradiation is toxic, we initiated a prospective phase II trial in August 2001 to test the safety and outcome of neoadjuvant CTX without radiation for resectable pancreatic cancer. Methods: Pts with cytologically confirmed resectable ductal adenocarcinoma of the pancreatic head were eligible for this phase II trial. Staging and restaging examinations included chest and abdominal CT-scan, endoscopic ultrasound with cytology, PET/CT and diagnostic laparoscopy. CTX consisted of four treatments of gemcitabine (1000mg/m2) and cisplatin (50mg/m2) every two weeks, and PD was planned at week 8. CA 19–9, prealbumin serum levels, and quality of life (QLQ- 30) were also determined before and after CTX. The primary study end-point was resectability based on re-staging examinations. Follow-up CT- scans were performed every six months. Results: Thirty-one pts entered this trial. Of these, 27 completed CTX and restaging until analysis. At restaging two pts had peritoneal metastases resulting in a resectability rate of 93% (25/27). No grade IV, and 7 transient grade III toxicities occurred in five pts. Median progression-free and overall survival after diagnosis were 9.2 months (95% CI 7.7–10.8) and 26.5 months (95% CI 15.2–37.7), respectively, for resected pts. After CTX, CA 19–9 serum levels were decreased by 48% (p=0.01). Moreover, the overall quality of life was increased by 24% (p=0.02). Prealbumin serum levels were abnormal in 40% of the pts on study entry, and normal in all but 89% after CTX (p=0.02). Conclusions: Neoadjuvant gemcitabine/cisplatin over two months is well tolerated and does not jeopardize resectability of adenocarcinoma of the pancreatic head. It offers several advantages including patient selection for surgery, improvements in the nutritional status and quality of life. A randomized trial comparing adjuvant and neoadjuvant+adjuvant treatment is being planned. No significant financial relationships to disclose.
Population based study of islet cell carcinoma
Authors: Mares J. , Eisner M. P. , Dagohoy C. , Phan A. , Rashid A. , Evans D. B. , Yao J. C. 
Published: March 2020

15103 Background: Little is known about the epidemiology and natural history of islet cell carcinoma. In this study, we examine the epidemiology, natural history, and prognostic factors impacting survival duration for islet cell carcinoma using population based registries. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program database (1973 - 2003 release April 2006) was used to identify cases of islet cell carcinoma using histology codes and tumor site. Results: 1,310 (619 women and 691 men) cases were identified. Median age at diagnosis was 59 years. The annual age-adjusted incidence in the periods covered by SEER 9 (1973–1991), SEER 13 (1992–1999), and SEER 17 (2000–2003) were 0.16, 0.14, and 0.12 per 100,000 respectively. The estimated 28-year limited duration prevalence on January 1, 2003 in the United States was 2,705 cases. Insulinomas (57%), glucagonomas (53%), and VIPomas (64%) were more likely to be located in the tail of the pancreas while gastrinomas were more likely to be located in the head of the pancreas (63%). Classified by SEER stage, localized, regional, and distant stages corresponded to 14%, 23% and 54% of cases. The median survival was 38 months. By stage, median survival for patients with localized, regional, and distant disease were 124 (95% CI, 80–168) months, 70 (95% CI, 54 - 86) months, and 23 (95% CI, 20 - 26) months respectively. By multivariate Cox proportional modeling, stage (P < 0.001), primary tumor location (P = .04), and age at diagnosis (P < 0.001) were found to be significant predictors of survival. Conclusion: Islet cell carcinomas account for approximately 1.3% of cancers arising in the pancreas. Most patients have advanced disease at the time of diagnosis. Despite its reputation of being indolent, survival of patients with advanced disease remains in the range of 2 years. Development of novel therapeutic approaches is needed. No significant financial relationships to disclose.
Correlation between the expression abnormalities of E-cadherin-β-catenin complex and lymph node metastasis (LNM) in early gastric cancer
Authors: Yoshii T. , Miyagi Y. , Nakamura Y. , Motohashi O. , Nishimura K. , Nakayama N. , Takagi S. , Kobayashi O. , Kameda Y. 
Published: March 2020

15105 Background: Therapy for early gastric cancer (GC) varies according to risk of LNM. When the possibility of LNM is very remote, the primary lesion can be resected by the minimally invasive endoscopic surgery only. Therefore, useful parameters predicting LNM are needed. E-cadherin, a component of the cell-cell junctional structure, is known to correlate with GC. In vitro, previous studies elucidated that disorders of cell-cell junction increased the potential of metastasis, and that phosphorylation of β-catenin by c-erbB-2 induced loss of membranous E-cadherin and β-catenin, resulting in junctional structure disorders. Here we evaluated significance of analysis of these molecules in LNM prediction in early GC. Methods: The clinicopathological features and immunohistochemical expressions of E-cadherin, β-catenin, and c-erbB-2 in the primary lesion were studied in 28 patients (LNM +ve group: 14, LNM1 -ve group: 14) selected from 272 patients who underwent radical surgery for early GC between April 2000 to March 2004 at our hospital. All the patients consented to use of their stomach tissues for the clinical study afterwards. Statistical analysis was performed by t-test or χ2 test. Results: The clinicopathological features showed no significant differences between both groups. Loss of the membranous E-cadherin was noticed in 12 (85%) of the 14 LNM +ve patients, and in 8 (57%) of the 14 LNM -ve patients (p=0.209). This result was more remarkable in the intestinal type GC as the corresponding figures were 83% (5 of 6 ) and 16% (1 of 6) (p=0.083), respectively. Loss of the membranous β-catenin also showed a remarkable similar trend in the intestinal type GC, and the corresponding figures were 100% (6 of 6) and 50% (3 of 6) (p=0.182), respectively. Two patients showed over-expression of c-erbB2 and nuclear accumulation of β-catenin, and both had intestinal type GC with LNM. Conclusions: These results suggested that the same molecular signal pathway - as in vitro - including E-cadherin, β-catenin, and c-erbB2 induced LNM in early GC (intestinal type). We concluded that analysis of the expressions of these molecules is useful for not only LNM prediction but also determination of the therapeutic modality especially in intestinal type early GC. No significant financial relationships to disclose.