tbuckley/cabot-search huggingface dataset:
Addition of bevacizumab to induction plus concomitant capecitabine-oxaliplatin (XELOX) chemoradiotherapy (CRT) in MRI poor prognosis locally advanced rectal cancer: Avacross study
Authors: M. Nogue, A. Salud, P. Vicente, C. Pericay, A. Arriví, J. M. Roca, F. Losa, J. Ponce, M. J. Safont, I. Guasch
Journal: Journal of Clinical Oncology (2009)

4100 Background: Concomitant CRT with 5-FU followed 6–8 weeks later by TME surgery is well accepted standard treatment for locally advancer rectal cancer. This approach focuses only into local control. Trimodal induction approaches with chemo, radiation and anti VEGFR therapy may induce additional tumor growth delay. Methods: Eligible patients (pts) had high-risk rectal adenocarcinoma defined by MRI: distal T3 at/below levators, T3 at any other level within 2 mm of mesorectal fascia, resectable T4 and any T3 with nodal metastases. We excluded pts with any antecedent of heart disease. Treatment consisted in four 21 day cycles of oxaliplatin 130 mg/m 2 d 1, bevacizumab 7.5 mg/kg d 1 and capecitabine 1000 mg/m 2 /12 h d 1–14. After 3–4 weeks they received concomitant RT (50.4 Gy in 28 fractions) with capecitabine 825 mg/m 2 /12 h plus bevacizumab 5 mg/kg, three biweekly doses. TME was planned 6–8 weeks after CRT. Primary end point was pathologic complete response rate with standarized pathology examination. Results: From July 2007 to July 2008, 47 pts were enrolled. Median age was 58 (30–78). Median KPS was 90%. Clinical stage was T3N1: 51.1%, T3N2: 25.5%, T4N0–2: 10.6%, T3N0: 8.5% of pts. 40 pts completed the induction phase: G 3–4 toxicity were diarrhea 12.7%, neutropenia 8.5%, peripheral neuropathy 6.3% and thrombocytopenia 4.2%.. 39 pts completed the CRT phase. Grade 3–4 toxicity were rectitis, linfopenia and hipertrigliceridemia in 2.5% of pts. Until now we have data on 35 resections, 2 with only one induction cycle. R0 resections were achieved in 34 pts (R1 resection in a patient with only one induction cycle). There were 7 wound complications and 10 pts required surgical reintervention. pCR were obtained in 13 pts (37,1 %, 95% CI:21.1–53.2) with 18 (51.4%) additional pts with only residual microscopic foci. There were two treatment related-deaths: one sudden death and one grade 4 diarrhea and diabetic ketoacidosis. Conclusions: Preliminary results show that our preoperative schedule appears feasible, with impressive activity level (pCR + Tmic of 88.5%), achieving downstaging in nearly all pts. Toxicity was manageable, nevertheless we stress caution with cardiac and GI events and surgical complications. No significant financial relationships to disclose.
A phase I/II study of S-1 and CPT-11 therapy for patients (pts) with metastatic gastric carcinoma (GC)
Authors: H. Uetake, M. Inokuchi, K. Sugihara, K. D. Danenberg, P. V. Danenberg, P. V. Danenberg
Journal: Journal of Clinical Oncology (2006)

14156 Background: S-1 was recently developed as a first line chemotherapy for the treatment of metastatic GC. We performed a phase I study of S-1 plus CPT-11 therapy for metastatic GC and reported that the maximum tolerated dose and the recommended dose (RD) of CPT-11 were 90 and 80 mg/m 2 , respectively. Objectives of the present trial were to estimate the response rate (RR) of this regimen. Methods: Eligibility criteria were as follows; histologically proven CRC with measurable metastatic lesions, PS 0–2, age &lt; 80, adequate organ functions, and written informed consent. No prior chemotherapy except adjuvant setting was allowed. S-1 was administered orally, 80 mg/m 2 /day on 14 consecutive days with 14 days’ rest for 4 weeks, and CPT-11 was infused at the RD in phase I trial on days 1 and 8. This schedule was repeated every 4 weeks. Results: Objective responses according to RECIST criteria were observed in 26 of the 42 pts (RR = 62%). Nineteen pts were with Grade 3 and 4 neutropenia and 10 with diarrhea Median survival time was 444 days. Intratumoral gene expression was analyzed using laser capture microdissection and RT-PCR method (Response Genetic Inc). Lower gene expression was observed in tumor cell of responder (P = 0.01). Conclusions: High RR and mild toxicity profile of S-1 plus biweekly CPT-11 therapy may be favorable for metastatic GC. No significant financial relationships to disclose.
Optimizing the delivery of chemotherapy in the setting of immunotherapy in a preclinical glioblastoma model
Authors: Dimitrios Mathios, Jennifer Kim, Jillian Phallen, Antonella Mangraviti, Chul-Kee Park, Debebe Theodros, Christopher Jackson, Tomas Garzon-Muvdi, Eileen Kim, Xiaobu Ye, Betty Tyler, Henry Brem, Drew Pardoll, Michael Lim
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Glioblastoma, despite the use of radiation and chemotherapy, remains vastly lethal. Cancer immunotherapy has entered the era of maturity with new compounds like anti-PD-1 FDA approved to treat advanced tumors. However, the use of immunotherapy in the setting of chemotherapy
Abstract 18765: PAR-1 Contributes to the Innate Immune Response to Viral Infection
Authors: Silvio Antoniak, Albert P Owens, Julie C Williams, Rebecca D Lee, Alice Weithäuser, Martin Baunacke, Patricia A Sheridan, Ronny Malz, Rafal Pawlinski, Burns Blaxall, Melinda A Beck, Ursula Rauch, Nigel Mackman
Journal: Circulation (2012)

Objective: Viral infections activate the blood coagulation cascade as part of the host defense response. Coagulation proteases, such as thrombin, induce cellular responses by cleaving protease-activated receptors (PARs). It has been proposed that infections are detected by a dual-sensor system consisting of PARs and Toll-like receptors (TLRs). In this study, we analyzed the role of PAR-1 in host defense against infection with coxsackievirus B3 (CVB3) and influenza A virus. Methods: Wild-type (WT) and PAR-1 deficient (PAR-1 -/- ) mice were infected with either CVB3 or influenza A (H1N1/PR8). The innate immune response, viral load and inflammation were was analyzed. Bone-marrow transplantation experiments were performed to identify the cellular source of PAR-1 contributing to the innate immune response to CVB3. In addition, we analyzed the effect of PAR-1 activation on TLR3-dependent induction of interferon-β and CXCL10 expression in culture cardiac fibroblasts. Results: PAR-1 -/- mice exhibited a reduced innate immune response to both viral infections that led to higher viral titers and inflammation compared to WT mice. PAR-1 -/- mice also exhibited increased CVB3-induced myocarditis. Bone marrow transplantation experiments demonstrated that PAR-1 on non-hematopoietic cells played a role in CVB3 infection, and mice overexpressing PAR-1 on cardiomyocytes had reduced myocarditis. Stimulation of PAR-1 on mouse cardiac fibroblasts enhanced p38 activation and TLR3-dependent induction of interferon-β and CXCL10. Conclusion: Our results indicate that activation of PAR-1 contributes in a p38-dependent manner to the innate immune response to viral infection. The use of PAR-1 inhibitors to reduce platelet activation in patients with cardiovascular disease may increase their susceptibility to virus infections.
Molecular classification of carcinoma of unknown primary by gene expression profiling from formalin-fixed paraffin-embedded tissues
Authors: M. G. Erlander, M. W. Moore, P. Cotter, M. Reyes, R. Stahl, H. Hamati, X.-J. Ma, K. Bloom, D. Sgroi, D. Baunoch
Journal: Journal of Clinical Oncology (2004)

9545 Background: Carcinoma of Unknown Primary (CUP) accounts for up to 10% of new cancer cases. CUP is defined as a biopsy-proven carcinoma with no identifiable source as determined by a series of analyses which include physical examination, blood and urine tests, X-ray, and tomography as well as examination of the biopsy via tumor morphology (H&E), and immunohistochemistry. Most CUP cases remain unresolved (∼75%) even at autopsy (20–40%). Therefore, we investigated the utility of gene expression profiling as an alternative method for the identification of CUPs. Methods: We have collected ∼400 primary and metastatic tumor biopsies representing over forty different tumor subtypes and have analyzed gene expression profiles generated using a ∼44,000 gene custom microarray optimized for FFPE samples. A second blinded study set of ∼150 FFPE biopsies are also being examined to determine the ability to discriminate between matched primary and metastatic disease (from a known primary) versus a second primary tumor. Results: Bioinformatics analyses of tumor subtypes of known origin define gene expression profile signatures that clearly discriminate between different tumor subtypes. We are currently analyzing samples with a known primary and a matched metastatic lesion, and comparing these signatures to those from samples with a second primary tumor. Conclusions: This study demonstrates the potential clinical utility of gene expression profiling for the identification of tumors of unknown primary, generating a molecular signature of over forty of the most common tumors encountered in the modern pathology laboratory. We believe this study represents an important advance towards improving the identification of CUPs as well as differentiating between metastatic stage disease versus a new primary tumor. No significant financial relationships to disclose.
A prospective study of the appearance-related side effects (ARSE) in 638 Japanese patients receiving cancer chemotherapy.
Authors: C. Shimizu, K. Nozawa, S. Yamamoto, M. Kakimoto, Y. Takahashi, A. Ito, H. Izumi, Y. Fujiwara
Journal: Journal of Clinical Oncology (2010)

e19516 Background: Little is known about ARSE of chemotherapy which may impact the self-esteem and social behaviors of cancer patients. The purpose of this study is to evaluate the pain of ARSE and its impact on quality of life (QOL) in cancer patients receiving chemotherapy. Methods: 753 patients receiving more than one cycle of chemotherapy at Ambulatory Chemotherapy Center in National Cancer Center Hospital were asked to answer a questionnaire asking their experience of ARSE (57 items including scars of surgery), non-appearance-related side effects (23 items) and appearance-related QOL. The pain of side effects was measured by score of 0 to 3 (0: no pain; 3 worst pain). Appearance-related QOL was assessed using the Derrifoid Appearance Score 59. The patients' concern about appearance and their ability to cope with change of appearance were also asked. Results: 638 patients (male 264, female 374; mean age 59.5 ± 11.7 yrs) responded to the questionnaire. The numbers of patients by cancer type were gastrointestinal 202, breast 175, hepatobilirary 69, hematological 60, lung 55, and others 78. Eighty percent of the patients had concern about appearance. The ranks of pain of side-effects were different by sex, cancer types and types of chemotherapy. In female patients, 4 of the top 10 painful side-effects were ARSE, whereas there was no ARSE among the top 10 in male patients. The pain score of ARSE was higher and QOL was lower in female than male (p<0.001), and younger than elderly patients (p<0.06) when restricted by chemotherapy regimen. Patients who experienced severe change of appearance had significantly worse QOL (p<0.001) and less social activities (p<0.001). Patients who were able to cope with change of appearance had significantly better QOL (p<0.001). Only 17% of the patients were satisfied with the information on ARSE, although 97% answered that it should be given from health care providers. Conclusions: Health care providers should be aware of ARSE and should give sufficient information to patients to support them cope with the change of appearance. No significant financial relationships to disclose.
Chromosome Band 1p36 Contains a Putative Tumor Suppressor Gene Important in the Evolution of Chronic Myelocytic Leukemia
Authors: Naoki Mori, Roberta Morosetti, Susanne Spira, Stephen Lee, Dina Ben-Yehuda, Gary Schiller, Raffaele Landolfi, Hideaki Mizoguchi, H. Phillip Koeffler
Journal: Blood (1998)
Is the blood-brain barrier relevant in metastatic germ cell tumors?
Authors: J. M. Azar, L. H. Einhorn, B. P. Schneider
Journal: Journal of Clinical Oncology (2007)

15618 Background: Metastatic germ cell tumors (GCT) are highly curable. Central Nervous System (CNS) recurrence can terminate a complete remission in other chemosensitive tumors such as small cell lung cancer due to the blood brain barrier (BBB). We document that the BBB can also be relevant in GCTs despite dramatic chemosensitivity. Methods: We present five cases of CNS only relapse in GCTs. None of these five patients had CNS metastases at the start of chemotherapy. Results: We have identified five unique patients from our large series of metastatic testicular cancer patients treated with chemotherapy. These patients were rendered free of disease with cisplatin- based chemotherapy only to relapse in the brain alone ( Table 1 ). This included one patient with good risk disease by the International Germ Cell Collaborative Group staging system (Patient #5). All patients had pulmonary metastases at diagnosis and a component of embryonal carcinoma. Three patients are alive without evidence of disease (NED) at 19, 32 and 8 months. One patient died of his disease (DOD) and one patient is alive with disease (AWD). Conclusion: The blood brain barrier is relevant in metastatic testicular cancer. [Table: see text] No significant financial relationships to disclose.
Burkitt lymphoma in children: The Israel Society of Pediatric Hematology Oncology retrospective study
Authors: M. Weyl Ben Arush, A. Hersalis Eldar, G. Abrahami, D. Attias, A. Ben Barak, R. Dvir, H. Gabriel, J. Kapelushnik, H. Kaplinsky, S. Vilk-Revel
Journal: Journal of Clinical Oncology (2009)

10051 Background: From 2000 to 2005, the Israel Society of Pediatric Hematology Oncology studied the results of the FAB-LMB 96 protocol in children with B cell lymphoma. Methods: Eighty eight patients (pts) were eligible, 63 boys, 25 girls, median age was 8.9 years. Fifty patients (57%) were classified as burkitt lymphoma, 5 (5.7%) as burkitt-like lymphoma, 22 (25%) as diffuse large B cell (DLBC), 9 (10.2%) as burkitt leukemia. Initial disease sites included the abdomen in 43%, head and neck in 45%, mediastinum in 7%. Stage I: 9.1%, Stage II in 28.4%, stage III in 45.5%, stage IV in 17%. Five pts had bone marrow involvement (BM) alone, 5 pts CNS alone and 4 both CNS and BM. Five children were treated according to group A, 69 pts group B and 14 pts group C. Results: At a median follow up of 3 years, Kaplan Meier for EFS and OS for all pts was respectively 88.6%, 90.9%, group A, 100%,100%, group B: 90%, 93%, group C 79%, 79%. In group A: there were neither events nor deaths in this group, 6 patients relapsed in group B, among them 4 patients had died, tumor lysis syndrome in 3 patients, death of toxicity in 1 patient. In group C, 3 patients had relapsed and died, no death of toxicity. EFS for LDH less then twice was 96.4%, EFS for LDH more than twice was 73.3% (p = 0.002). OS according to primary site: bone and ovary (100%), head and neck (95%), abdomen (92%) and mediastinum (50%) (p = 0.003). All of the mediastinal tumors were of DLBC origin, but when comparing the DLBC to other histologies, no significant difference in outcome were found.(DLBC: 81.8%, other B line: 90.9%). The OS for Arab ethnic origin is 79.2%, OS for Jewish is 95.3% (p = 0.02). Conclusions: In nonresected mature B cell lymphoma of childhood and adolescence with no BM or CNS involvement, a 93% cure rate was achieved. Patients with primary DLBC mediastinal mass had a significantly reduced overall survival, indicating the need for a different therapeutic approach. No significant financial relationships to disclose.
A multicenter phase II of S-1 in gemcitabine-refractory biliary tract cancer.
Authors: E. Suzuki, M. Ikeda, T. Okusaka, S. Nakamori, S. Ohkawa, T. Nagakawa, N. Boku, H. Yamagimoto, K. Sugimori, J. Furuse
Journal: Journal of Clinical Oncology (2010)

4145 Background: Gemcitabine (GEM)-based chemotherapy has been used as the first-line treatment for advanced biliary tract cancer worldwide. However, no standard regimens have been established after disease progression. In a previous phase II trial, S-1 has been reported to have considerable efficacy, yielded a response rate of 35.0% in chemo-naive patients (pts) with advanced biliary tract cancer. This study evaluated the efficacy and safety of S-1 in patients with GEM-refractory biliary tract cancer. Methods: The eligibility criteria were pts 1) with pathologically-proven biliary tract cancer, 2) who were confirmed to show disease progression while receiving GEM-based chemotherapy, 3) with an ECOG performance status 0 to 2, 4) aged 20 to 79 years, 5) with measurable metastatic lesions, 6) with adequate hematological, renal and liver functions, and 7) who provided written informed consent. Each treatment cycle consisted of S-1 administered orally at the dose of 40 mg/m2 twice daily for 28 days, followed by a rest period of 14 days. The cycle was repeated until the appearance of disease progression or unacceptable toxicity. The primary endpoint of the study was objective response, and the secondary endpoints included toxicity, progression-free survival (PFS) and overall survival (OS). Results: Forty one pts were enrolled from 8 hospitals between June 2007 and September 2008, and of the41, 40 were assessable. There were 3 confirmed partial responses (7.5%), and 22 pts (55%) with stable disease. The median PFS and OS were 2.5 months and 7.5 months, respectively. Toxicity was generally mild and the main grade 3 or 4 toxicities were anorexia (10.0%), anemia (7.5%), mucositis (7.5%), hypoalbuminemia (5.0%) and pneumonia (5.0%). There were no treatment-related deaths. Conclusions: S-1 administered as single-agent chemotherapy in patients with gemcitabine-refractory biliary tract cancer appears to be well tolerated, however, its efficacy is modest. In view of the favorable toxicity profile, it would be of interest to evaluate the effect of this drug administered in combination with other agents to improve the therapeutic results. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Taiho Pharmaceutical Taiho Pharmaceutical
Risk and protective factors for midgut carcinoid tumors: Multicenter case-control study of prospectively evaluated patients.
Authors: M. Rinzivillo, G. Capurso, D. Campana, N. Fazio, F. Panzuto, C. Bestani, E. Merola, M. Falconi, P. Tomassetti, G. delle Fave
Journal: Journal of Clinical Oncology (2010)

e14533 Background: Midgut carcinoids (CTs) have a rising incidence ≈ 1/100,000. Few studies investigated risk factors for their occurrence, reporting a possible role of family history (FH) of CTs and colorectal cancer (CRC), smoking. Our aim is to identify risk factors for the occurrence of CTs in a prospectively evaluated cohort. Methods: Multicentre case- control (C-C) study. Patients with diagnosis of CTs, without familial syndromes. Controls with nonneoplastic/nonchronic disorders. All interviewed on demographics and potential risk factors. Cases and controls compared by χ2 or Student's t-test. Explanatory variables analyzed by simple logistic regression analysis. Multiple logistic regression analysis with a stepwise variable-selection procedure, p < 0.05 significant. Results: 190 CTs (54.7% M; mean age 50) and 693 controls (50.3% M; mean age 49.5) enrolled. Of CTs 137 (72.1%) without carcinoid syndrome, most patients had WDEC (170 89.4%), and 75% metastatic disease at diagnosis. Smoking (44.3% vs. 34% p = 0.02), heavy smoking (> 20 pack/year) (23% vs. 14,4% p = 0.006) and high alcohol intake (> 21 drinks/week) (7.8% vs. 2.8% p = 0.005) more frequent in CTs. No difference regarding BMI, gynaecological nor medical history/medications, but for use of ASA, which seemed more frequent amongst controls than CTs (3.3% vs 0.5% p = 0.07). First-degree FH of any cancer more frequent amongst CTs (37.8%) than controls (30% p = 0.04). Of different cancer sites CRC first-degree FH was the most significant (8.9% CTs vs. 4.3% controls p = 0.01). At univariate logistic regression analysis, first-degree FH of any cancer (OR 1.4 95%CI 1.0-1.9), CRC first-degree FH (OR 2.1 95%CI 1.1-4.0) ever (OR 1.6 95%CI 1.1-2.2) and heavy smoking (OR 1.8 CI 1.2-2.7) were significant risk factors, use of ASA protective (OR 0.1 95%CI 0.02-1.1). Multivariate analysys included ever smoking (OR 1.5 95%CI 1.1-2.2), first degree CRC FH (OR 2.1 95%CI 1.1-4) and use of ASA (OR 0.1 95%CI 0.0-0.9). Conclusions: The present C-C study identified CRC FH and smoking as independent risk factors for the occurrence of CTs, and use of ASA as protective. These data partially in keeping with previous studies, suggest an overlap with risk and protective factors for CRC. No significant financial relationships to disclose.
Breast cancer recurrence and related mortality in U.S. pts with early breast cancer
Authors: L. Lamerato, S. Havstad, S. Gandhi, D. Jones, R. Chlebowski
Journal: Journal of Clinical Oncology (2005)

738 Background: An understanding of the relationship between breast cancer (BC) recurrence and mortality in pts with early BC is important. The objective of this study, therefore, was to evaluate this relationship among a mid-western health system population. Methods: A retrospective cohort study of 1616 pts (mean age 60 yrs) with early BC (stage I and II) was conducted using data from a large integrated health care system. Information on demographics, disease characteristics/treatment, evidence/type of recurrence, and death was obtained. Kaplan-Meier estimates were used to compare overall and BC-related mortality between recurrence types, and also between each recurrence type and a control group without recurrence. For each comparison, hazard ratios (HR) were estimated after controlling for baseline covariates. Results: During a median follow-up of 44.5 (range 6.1–98.3) months, there were 192 (11.9%) recurrence events (26.1% loco-regional, 15.6% contralateral, 58.3% distant) and 188 (11.6%) deaths due to any cause, of which 85 (5.3% of study population) were BC-related. Compared with the non-recurrence group, the distant recurrence group showed the highest risk of death (HR=13.6, p<.001), followed by the loco-regional recurrence group (HR=4.5, p<.001), and the contralateral recurrence group (HR=3.0, p=.01). The 5-year overall survival probability for distant, loco-regional, contralateral recurrence, and pts without recurrence was 41.3%, 59.3%, 83.4%, and 91.7%, respectively. Median time to all-cause mortality for pts with distant, loco-regional, and contralateral recurrence was 41.2, 76.9, and 89.5 months, respectively. A similar trend was observed for BC-related mortality, with a significantly higher risk of BC-related death in the distant recurrence group vs women with loco-regional recurrence (HR=3.6, p<.001). Conclusion: The study shows that BC recurrence, irrespective of type of recurrence, is associated with increased mortality in pts with early BC. This effect on mortality is substantially more pronounced in pts with distant recurrence. Therapies shown to reduce the risk of BC recurrence are likely to have a significant beneficial effect on survival in pts with early BC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca