bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infectious complications associated with alemtuzumab treatment
Authors: Siddique S. A. , Fowler N. , Asatiani E. , Mavromatis B. , Cohen P. , Kessler C. M. , Cheson B. D. 
Published: March 2020

13504 Introduction: We report our single institutional experience of ICs associated with alemtuzumab treatment. Methods: Patients (pts) who received alemtuzumab were identified by review of the GUH pharmacy database. All ICs occurring from initiation of alemtuzumab until death or end of follow up as of January 3, 2007 were reviewed and categorized as opportunistic (OI) or non- opportunistic (NOIs). Pts who received hematopoetic stem cell or solid organ transplantation subsequent to alemtuzumab (n=33) or who could not tolerate test doses of alemtuzumab (n=1) were excluded from analysis. Results: Data were reviewed for 16 pts treated with alemtuzumab from February 2003 to September 2006. Median age was 60 years (range 40–78); with 4 females and 12 males. Fifteen pts had chronic lymphocytic leukemia (CLL), and 1 had acute lymphoblastic leukemia (ALL). Median follow-up after starting alemtuzumab treatment was 462 days. Pts with CLL had an average of 2.4 prior treatments (range 1–6). The pt with ALL received alemtuzumab as part of multi-agent intensification chemotherapy regimen. Alemtuzumab was administered subcutaneously, 30 mg three times a week. Median of 29 doses (range 7- 45) were given. Among CLL pts there was 1CR, 8 PRs and 6 PDs (RR 60%). Pneumocystis jirovenci (PCP) and herpersvirus (HSV) prophylaxis was given to 15 (93%) pts. Cytomegalovirus (CMV) surveillance was performed for all. Absolute lymphocyte count (ALC) <1000/μL developed within 5 weeks in 12 (75%) pts. Median ALC at 8 weeks was 155/μL (range 0–18,612). Thirteen OIs were diagnosed in 9 (56%) pts including asymptomatic CMV viremia (n=5), PCP (n=2, one pt did not received PCP prophylaxis), invasive pulmonary aspergillosis (n=2), disseminated histoplasmosis (n=1), localized HSV (n=1), disseminated herpes zoster (n=1), and cerebral acanthamebiasis (n=1). Seven NOIs were noted in 6 pts including bacterial pneumonia, sinusitis, endocarditis and pseudo-membranous colitis. Mortality secondary to ICs was 31%. There was no correlation between ICs and age, duration of lymphoproliferative disorder, number of prior treatments, cumulative dose, response to alemtuzumab, or ALC. Conclusion: Despite adequate prophylaxis, ICs secondary to alemtuzumab are more frequent and diverse than previously reported in clinical trials. No significant financial relationships to disclose.
Is farnesyltransferase inhibitor effective as adjuvant or neoadjuvant therapy in orthotopic implantation of hamster pancreatic cancer
Authors: Lima E. M. , Morioka C. Y. , Costa F. P. , Saito S. , Huang C. C. , Watanabe A. 
Published: March 2020

14153 Background: p21-Ras participates in signalling events from membrane tyrosine kinase receptors and a variety of intracellular biochemical pathways to downstream therapeutic strategy.Farnesyl transferase inhibitors (FTI) block the main post-translational plasma membrane and subsequent activation of downstream effector.A curative resection model in Syrian golden hamsters has been developed previously. Aim: To evaluate the effectiveness of FTI as adjuvant or neoadjuvant therapy in hamster experimental pancreatic cancer model. Materials and Methods: HaPT-1,a cell line derived from nitrosamine induced pancreatic cancer was used in these experiments.MTT and MTT agarose were performed.Subcutaneous implanted tumor was resected in exponential phase and tissue was implanted into the pancreas.At Day 7 or Day 14, partial pancreatectomy and splenectomy were performed.Hamsters were divided in 7 groups:1.Positive control (PC,n=5),2.Only FTI (FT,n=5),3.Neodjuvant therapy after surgical resection at Day 7 (NT-R7,n=10),4.Adjuvant therapy after resection at Day 7 (AT-S7,n=10),5.Neoadjuvant therapy after resection at Day 7 (NT-S14,n=10),6.Adjuvant therapy after resection at Day 14 (AT-S14,n=10), and 7.Only surgery at Day 14 (SR,n=5).FTI was administered for one week. In FT and NT groups, drug was administered 3 days after orthotopic implantation.Body weight and side effects were recorded.Fourteen days after the surgical resection, sacrifice was done.Four animals of each group were left to study the survival.After 180 days, living hamsters were sacrificed. Resected and necropsied specimens were sent to histopathological analysis. Results: Successful rate of implantation was 100%.PC,FT,NT-S7,AT-S7,NT-S14,AT-S14,and SR survived in average 82,103,119,134,123,132,and 139 days.Two hamsters of AT-S7 (20%),two of AT-S14 (20%),and two of SR (40%) were alive until 180 days.Intra operatory bleeding was higher in NT groups.Loss of body weight was present in all FTI treated groups. Conclusions: Farnesyltransferase inhibitor showed not to be effective in the curative treatment of orthotopically implanted tumors. It may be used to increase the survival time as adjuvant therapy. No significant financial relationships to disclose.
Relevance of a medicosurgical strategy combining cetuximab and chronomodulated (Chrono) chemotherapy (chemo) with metastases resection as 3rd line treatment for patients (pts) with metastatic colorectal cancer (MCRC)
Authors: Karaboue A. , Bouchahda M. , Adam R. , Innominato P. , Bralet M. P. , Moreau T. , Hauteville D. , Guettier C. , Levi F. 
Published: March 2020

14505 Background: Metastases surgery offers long tem survival for pts with chemo-downstaged MCRC (Adam et al. Ann Surg 2004). The relevance of this medicosurgical strategy was investigated in pts given cetuximab (Cetux) and Chrono after chemo failure. Methods: 56 pts with progressive MCRC on prior chemo received Cetux (400 mg/m2 on 1st dose then 250 mg/m2/week) and q2w Chrono based on irinotecan (34 pts), oxaliplatin (14 pts) or both (8 pts). Toxicity grades (G) and response were assessed q2w and q8w, respectively. Tumour EGFR was determined by immunohistochemistry (all pts) and gene copies by fluorescence in situ hybridisation (27 pts). Metastases surgery was attempted whenever complete resection was foreseen. Results: Median of 3 prior chemo (1 to 8); median age: 61 years (35 to 79); M/F: 34/22; WHO PS 0/1/2/3: 37/14/4/1; colon/rectum: 32/24; M sites 1/2/=3: 15/22/19; liver/lung: 45/40. EGFR was detected in the tumor of 39 pts (69.6%). 3 pts had G4 allergy. 53 evaluable pts received a median of 5 courses of Cetux-Chrono (1–22). G2–3 acneiform rash occurred in 36 pts (67.8%; G3: 30.4%). Main G3–4 toxicities were diarrhea (26.5%), neutropenia (23.1%) and neuropathy (22.6%). The objective response rate (ORR) was 32% [95% CI, 19.4 to 44.6] (13 PR and 3 CR). ORR was correlated positively with acneiform rash (p= 0.019) but negatively with the detection of EGFR+ tumor cells (0%, ORR=54.5%; 1–10%, 33%; >10%, 16.7%; p = 0.044). No EGFR amplification was documented including 8 OR. Median progression-free survival (PFS) and overall survival were 5.1 [3.2–6.9] and 13.9 months [6.5–21.3] respectively. Metastases surgery was performed in 10 pts (8 R0, 2 R1) after 3–15 courses of Cetux-Chrono as 2nd-5th line. Median PFS in resected pts was 11.7 months [5.8–17.6], with a survival estimate of 80% at 21 months. Conclusions: Cetux-Chrono safely reverted MCRC resistance and allowed successful metastases resection in 17.8% of these pts, like 1st line chemo. This medicosurgical strategy impacted favourably on long term survival, despite its application as 3rd treatment line. Supported by ARTBC, Hôpital Paul Brousse, Villejuif, France No significant financial relationships to disclose.
Baseline and temporal patterns of fatigue predict pathological response in patients treated with preoperative chemoradiation therapy (CRT) for rectal cancer
Authors: Delclos M. , Krishnan S. , Mendoza T. , Lin E. , Vadhan-Raj S. , Das P. , Crane C. , Zhang Y. , Cleeland C. , Janjan N. 
Published: March 2020

14522 Background: We investigated whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathological response, a surrogate for treatment outcome. Methods: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Most patients had T3 tumors (94%) and hemoglobin > 12 (85%). Symptom burden was prospectively assessed prior to (baseline) and weekly during CRT by a patient self-reported questionnaire, the MD Anderson Symptom Inventory (MDASI). Survival probabilities were estimated non-parametrically using Kaplan-Meier’s product limit method. Lowess curves were plotted for symptom burden across time. Logistic regression was used to determine whether symptom burden levels predicted for pathological response. Results: Among 51 patients evaluable for pathological response, 9 patients (18%) achieved pCR, and 26 patients (51%) had TDS. The actuarial rates of local control (LC), disease-free survival (DFS), and overall survival (OS) at 2 years were 93%, 76%, and 98%, respectively. Patients with TDS had lower levels of fatigue at baseline and at completion (week 5) of CRT compared to those without TDS (p = 0.03 for both). A similar trend was not observed for other symptom burden parameters of pain, sleep disturbance, appetite, nausea, or feeling of sadness. Evaluation of the potential effect of symptom burden on pCR, LC, DFS, or OS was not possible because of the low number of events during the 2-year median follow-up. Conclusions: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathological response, as gauged by TDS. Unlike studies that have documented improved quality of life among responders, our study demonstrates the converse, i.e. fatigue, a measure of symptom burden, independently predicted for tumor response. This provocative finding could potentially be used to stratify patients into prognostic groups, influence treatment decisions, and/or modify treatment. An evaluation of changes in cytokine profile during CRT is ongoing to determine the molecular basis of this phenomenon. No significant financial relationships to disclose.
Serum REG4 protein in pancreatic cancer as a tumor marker: A prospective study
Authors: Sawaki A. , Takayama R. , Mizuno N. , Tajika M. , Hoki N. , Sayed Z. E. , Matsuo K. , Nakagawa H. , Nakamura Y. , Yamao K. 
Published: March 2020

15063 Background: Pancreatic cancer (PC) shows the worst mortality rate in common malignancies, with 5-year survival rate of 4%. The only way to cure the disease is surgical resection of early stage PC. Establishment of a screening strategy to detect early stage PC is eagerly expected. REG4, a member of the regenerating islet-derived (REG) family, are secreted proteins that play a role in tissue regeneration and inflammation in digestive organs. We reported overexpression of REG4 in PC cells and serum, and preliminary data of the serum REG4 level of pancreatic disease patients including PC patients. We conducted a prospective study to evaluate the role of serum REG4 in PC. Methods: The series included 57 patients diagnosed pathologically as PC between November 2004 and December 2005. Serum REG4 was quantified by standard sandwich ELISA (Enzyme Linked Immunosorbent Assay) using original kit (MBL116: provided by Medical and Biological Laboratories Co., LTD, Japan) before treatment. The upper limit of the test was set at 3.52ng/ml and was based on studies of serum from 48 healthy control subjects. Results: With a specificity of 100%, the diagnostic sensitivity and accuracy were 63.2% and 80.0%, respectively. The ROC (receiver operating characteristic) analysis showed that area under the curve was 0.91. REG4 levels were a significant differences between PC and control (p<0.001), between each T stage and control (T1,T2, T3 or T4 v control), and between each TMN stage and control (stage 1, stage 2, stage 3 or stage 4 v control), but were not a statistical significance with T stage (T1 v T2 v T3 v T4), M stage (M0 v M1) or TNM stage (stage 1 v stage 2 v stage 3 v stage 4) in PC patients. The diagnostic sensitivity of carcinoembryonic antigen (CEA>5.0ng/ml) and carbohydrate antigen19–9 (CA19–9>50U/ml) was 56.5% and 68.4%, respectively. No significant correlation was demonstrated between REG4 and CA19–9 (coefficient of correlation [rs]=0.45). Conclusions: This study shows the potential of serum REG4 as a screening test for PC, especially for early PC. REG4 is considered to be a more useful marker in combination with CA19- 9. No significant financial relationships to disclose.
Significance of galectin-3 immunohistochemistry , clinical characteristics, and liver imaging in differentiating intrahepatic cholangiocarcinoma from adenocarcinoma liver metastasis
Authors: Thamrongwitsawa A. , Kanngurn S. , Tanutit P. , Khow-Ean U. , Sunpaweravong P. 
Published: March 2020

15120 Background: Difficulties remain in distinguishing intrahepatic cholangiocarcinoma from adenocarcinoma liver metastasis , therefore specific immunohistochemistry markers are still needed. Galectin-3 is a beta-galactoside-binding protein and has been reported as a tissue marker in many neoplasms, including cholangiocarcinoma. Adding Galectin-3 to Cytokeratin immunohistochemistry may provide more definitive diagnosis to these conditions. Methods: Histological slides of intrahepatic cholangiocarcinoma and adenocarcinoma liver metastasis were reviewed independently by 2 pathologists to confirm diagnosis. Immunohistochemical staining was done with primary antibodies for Galectin-3 (NCL-GAL3), Cytokeratin-7 (CK-7) and Cytokeratin-20 (CK-20) in paraffin embedded tissues. The extent of Galectin-3 staining was categorized as 0% (none), 1–25% (weak), 26–65% (moderate), and > 65% (strong) positive of tumor cells. Clinical characteristics and liver imaging of all patients were also reviewed. Results: Thirty-three patients were evaluated , 17 cholangiocarcinoma and 16 adenocarcinoma liver metastasis. Seventy-five percent of cholangiocarcinoma strongly expressed Galectin-3 whereas 56% of adenocarcinoma liver metastasis did. CK-7 expression was found in 47% of cholangiocarcinoma and CK-20 41%. In colorectal liver metastasis, 6 of 7 patients (85%) were negative for CK-7 and positive for CK-20. When correlated with patient characteristics, cholangiocarcinoma tended to occur in patients who were older than 55 years. Regarding liver imaging, multiple liver masses without intrahepatic bile duct dilatation correlated with adenocarcinoma liver metastasis. Conclusion: Adding Galectin-3 immunohistochemistry may benefit for differentiating intrahepatic cholangiocarcinoma from adenocarcinoma liver metastasis. Further study in a larger series is encouraged to better define role of this protein in cholangiocarcinoma diagnosis. No significant financial relationships to disclose.
A phase II multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer
Authors: Ohkawa S. , Amano A. , Ueno M. , Miyakawa K. , Sugimori K. , Tanaka K. , Kida M. 
Published: March 2020

15129 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 trial and reported the results of the phase I trial last year. And this phase II study evaluated the efficacy and feasibility. Methods: The subjects had unresectable pancreatic ductal cancer. Eligibility criteria were pathologically-proven, Karnofsky performance status 80 to 100%, age 20 to 74 years, adequate hematological, renal, and liver functions and written informed consent. The method of administration was single administration of GEM on the first day of the week 1000 mg/m2, with concurrent administration of S-1 at 80 (<1.5 m2) to 100 (=1.5 m2) mg/day × 7 days, repeated every other week until the progressive disease or life threatening adverse events. This administration dose was determined from the result of the phase I study. The primary endpoint was median survival time. And the secondary endpoints were the overall response rate and the toxicities. Results: 40 patients(pts) were enrolled. Average age was 62.9±8.3 years (34–73 years). Thirty nine pts were conducted this therapy except one who refused this study before the start of administration. Thirty eight pts were evaluable for response, partial response, stable disease, progressive disease were observed in 7 (17.5%), 21 (52.5%) and 10 pts (25.0%), respectively. The median survival time at this stage is 276±51 days in this ongoing study. Grade 3 and 4 toxicities were mainly leucocytes(10 pts), neutrophils(8 pts) and anorexia(6 pts). Conclusions: The GEM plus S-1 combined chemotherapy is effective and feasible in patients with advanced pancreatic cancer. No significant financial relationships to disclose.
Induction cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy in locally advanced esophageal cancer: A single institution’s initial clinical experience
Authors: Harper J. L. , Shirai K. , Sharma A. K. , Montero A. J. , Hoffman B. J. , Reed C. E. , Sherman C. A. 
Published: March 2020

15151 Background: Phase I and Phase II trials of induction Cisplatin (C) and Irinotecan (I) followed by concurrent C+I and radiotherapy (RT) have produced encouraging clinical and pathologic response rates in esophageal cancer. However, to date published data detailing clinical outcome with this regimen is limited. Methods: A retrospective review of 17 patients with locally advanced esophageal cancer was performed to characterize toxicity and outcomes for this regimen in our institutional experience. Patients were treated during the period from August 2003 to July 2006 and staged comprehensively with EUS, CT and PET. Induction therapy with weekly I (65mg/m2) and C (30mg/m2) was administered (wks1,2,4,5). Those without progression received weekly I (65mg/m2) and C (30mg/m2) (wks 8,9,11,12) concurrent with RT. Patients considered surgical candidates based on pre- treatment clinical stage, medical co-morbidities, and pre-operative re-staging were offered an esophagectomy. Results: The patient demographics were as follows: 15 men, 2 women, median age 63 (45–76), white 53%, black 47%, adenocarcinoma 59%, squamous cell carcinoma 41%, 47% stage T3N1, 94% node positive, 6% M1a, and 29% T4 primary tumors. The mean RT dose was 50.4 Gy and median number of elapsed days of RT was 43 days. All patients completed induction C+I. Grade 3–4 hematologic toxicity (CTC v3.0)neutropenia (47%), anemia (6%), thrombocytopenia(18%). One patient died of a TE fistula 22 days after completing therapy. Two patients (12%) progressed during therapy. An esophagectomy was performed on 41% (7/17) of patients; 6 of 7 were R0, 71% (5/7) were downstaged, 14% (1/7) pCR. At median follow-up of 15 months, 8/17 (47%) pt are alive NED, 3/17 are alive with disease, 3/17 dead of disease and 3/17 are dead of other causes. Median DFS is 7 months and median local RFS is 7 months. Median OS has not been reached at 15 months. Conclusions: In this population with very advanced disease, I+C+RT have produced promising OS and local control outcomes with greater toxicity than in previously reported experiences with this regimen. No significant financial relationships to disclose.
Impact of BRCA 1/2 testing: Body image, sexual functioning, and quality of life (QOL)
Authors: Sun C. C. , Westin S. N. , Lu K. H. , Schmeler K. M. , White K. G. , Daniels M. S. , Arun B. K. , Peterson S. K. , Bodurka D. C. 
Published: March 2020

1525 Background: Management strategies for women at high risk of breast and ovarian cancer (OVCA) may affect sensitive QOL issues. Methods: As part of a larger study, 540 women who underwent testing for BRCA 1/2 prior to July 2005 were sent follow- up surveys, including FACT-Endocrine Symptom subscale (FACT-ES), Sexual Activity Questionnaire (SAQ), and a modified Body Image Scale. Chi-square, Mann-Whitney and Kruskal-Wallis tests were used to analyze the data. Results: To date, 309 patients (pts) have responded. Pts with previous oophorectomies were excluded (n=68). The final analysis included 241 pts categorized into 4 groups: Group 1=no breast CA, no prophylactic (proph) surgery (n=39); Group 2=no breast CA, + proph surgery (either proph oophorectomy (PO), proph mastectomy (PM), or PO+PM) (n=20); Group 3= + breast CA, no PO or PM (n=90); and Group 4= + breast CA, + proph surgery (n=92). Median age at time of survey = 50 yrs. Median age at time of PO = 46 yrs. Of 65 BRCA + pts, 36 chose PO, while 32/176 BRCA- pts chose PO (p<.001). 155 pts reported being sexually active at time of survey. Women with PO (n=68) had more endocrine symptoms by the FACT-ES vs pts who chose screening (n=173) (p=.005). Women in Group 2 reported more endocrine symptoms compared to all other women (p=.02). The same trend was noted for sexually active women only (p=.06). There were no differences in activity or pleasure measured by the SAQ between women with PO vs screening; pts with PO reported higher levels of pain/discomfort (p=.04). Women in Group 1 reported the lowest level of pain/discomfort (p=.004) and highest level of pleasure. Higher levels of discomfort and less sexual activity were reported by women with breast CA vs those without breast CA (p<.001; p=.05). Women in Group 3 had the most negative body image while Group 2 had the most positive (p=.03). Women who chose screening reported a more negative body image vs women with PO (p=.01). Pts with breast CA had more negative body image scores than women without breast CA (p=.06). Conclusions: Choice of management strategy and personal hx of breast CA appear to influence sexual functioning, endocrine symptoms and body image in women at high risk of breast and OVCA. Baseline assessment of these factors and continued dialogue are critical aspects of comprehensive care for these women. No significant financial relationships to disclose.