tbuckley/cabot-search huggingface dataset:
Efficacy and toxicity of two schedules of R-CHOP plus bortezomib in front-line B lymphoma patients: A randomized phase II trial from the Groupe d’Etude des Lymphomes de l’Adulte (GELA)
Authors: N. Mounier, V. Ribrag, C. Haioun, G. Salles, J. Golfier, M. Ertault, C. Ferme, J. Briere, P. Brice, E. De Kerviler, C. Gisselbrecht
Journal: Journal of Clinical Oncology (2007)

8010 Background: Bortezomib is the first proteasome inhibitor that showed promising activity in hematologic malignancies. In Jan 2005, we initiated a phase II randomized trial to evaluate front-line R-CHOP + bortezomib in B lymphoma pts. Methods: 6 cycles of standard R-CHOP (d1=d21) were planned, pts were randomized between 2 schedules of bortezomib: arm A (d 1,4,8,11), arm B (d 1,8). For the first 24 pts (step1), bortezomib was administred at 1 mg/m 2 in arm A and 1.3 mg/m 2 in arm B. For the next 24 pts (step2), it was increased at 1.3 mg/m 2 and 1.6 mg/m 2 respectively. G-CSF and EPO supports were allowed. Primary endpoint was CR rate after 6 cycles. Results: The trial was closed in Apr 2006 after inclusion of 49 pts. Sex ratio M/F was 28 /21. Median age: 63 years [32–76]. Pathology: 4 Lymphoplasmocytic, 4 small lymphocyte, 8 MZL, 2 Malt, 11 FL , 7 FL with histological transformation, 4 Mantle cell and 9 DLBC without adverse factor. Performance status 2–4: 4 pts; stage 4: 33 pts; LDH&gt;N: 16 pts and IPI 2–3: 18 pts. According to triangular-test interim analysis (Jan 2006), arm A was closed at 20 pts (11 step1, 9 step2). 29 pts received arm B (10 step1, 19 step2). 290 cycles of R- CHOP and 819 injections of bortezomid were given. In arm A, 5/20 pts received less than 90% of scheduled dose of bortezomib (all in step2); in arm B, 7/29 pts (2 step1 and 5 step2). Grade 3–4 thrombopenia occurred in 14% of cycles (35% arm A, 0% arm B, 14% step2), Grade 3–4 leucopenia in 41 % (35% arm A, 45% arm B, 43% step2). Neurological toxicity occurred in 21 pts: grade 2 in 11 (1 arm A, 10 arm B, 9 in step2) and grade 3–4 in 10 (5 arm A, 5 arm B, 9 in step 2). 6 of them were considered as serious adverse events. Other grade 3–4 toxicities were 1 constipation (1 arm B, step2), 3 infections (2 arm A, 1 arm B, 2 step 2) and 2 cardiac events (1 arm A, 1 arm B). 48 pts were evaluable for response: 40 achieved CR/CRU: 18/20 in arm A, 22/28 in arm B. There were 5 PR (1 arm A, 4 arm B), 1 SD (arm A) and 2 PD (arm B). 19/21 pts achieved CR in step 1 and 21/27 in step 2. After 1 year median follow up, OS was 100% and EFS 80%. Conclusions: R- CHOP+Bortezomid is an effective regimen with 83% CR rate. However, the higher doses of bortezomib lead to severe neuropathy and suggest that association with vinca alcaloides should be avoided. No significant financial relationships to disclose.
Patient surveillance after curative-intent surgery for rectal cancer
Authors: W. E. Longo, A. E. McGarry, S. R. Gammon, E. M. Grossmann, K. S. Virgo, K. Ode, R. A. Audisio, U. S. Shariff, T. Papettas, F. E. Johnson
Journal: Journal of Clinical Oncology (2004)

3661 Background: Follow-up of patients with rectal cancer after potentially curative primary therapy has significant financial and clinical implications for patients and society. The ideal monitoring regimen is unknown. Methods: We evaluated the self-reported practice patterns of a large group of experts. The 1,795 members of the American Society of Colon and Rectal Surgeons (ASCRS) were asked, via a detailed questionnaire, how often they request 14 discrete follow-up modalities (office visit, serum CEA level, CBC, liver function tests, sigmoidoscopy, colonoscopy, chest x-ray, intra-rectal ultrasound, abdomen/pelvis CT, chest CT, abdomen/pelvis MRI, positron-emission tomography, bone scan, and CEA scan) in their patients treated for cure with TNM stage I, II, or III rectal cancer over the first 5 post-treatment years. Results: Thirteen envelopes were returned unopened; 566 of the remaining 1,782 ASCRS members (32%) responded and 347 of these (61%) provided evaluable data. Members of the ASCRS often follow their own patients post-operatively rather than delegating this to others. Office visit is the most frequently requested item for each of the first 5 post-operative years (mean ± SD = 3.8 ± 2.7 visits in post-operative year 1 after radical surgery for stage I lesions, diminishing to 1.5 ± 1.0 visits in year 5). Colonoscopy is requested 0.9 ± 0.7 times in year 1 and 0.5 ± 0.7 times in year 5. Strategies for patients with stage II and III lesions are similar to those for stage I lesions. Conclusions: There is substantial variation in follow-up intensity among these experts. The reported surveillance strategies rely most heavily on relatively simple and inexpensive tests, but endoscopy and imaging modalities are also used regularly. The observed variation in the intensity of post-operative monitoring is of concern; investigation of the source(s) of this variation is warranted. No significant financial relationships to disclose.
Unrelated-donor bone marrow transplantation for Philadelphia chromosome-positive chronic myelogenous leukemia in children.
Authors: A S Gamis, R Haake, P McGlave, N K Ramsay
Journal: Journal of Clinical Oncology (1993)

PURPOSE Bone marrow transplantation (BMT) for Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML) results in a 55% to 64% disease-free survival (DFS) rate in 20% to 30% of cases with a matched-sibling donor (MSD). Studies that include primarily adults with CML, using unrelated-donor (URD) BMT, have expanded this option to those without an MSD. We review and compare the efficacy of URD and MSD BMT in children with Ph1 CML. PATIENTS AND METHODS Eleven children with URD BMTs were reviewed and compared with 11 children with MSD BMTs for Ph1 CML. Among the URD BMT recipients, there were three with fully matched marrows and 10 with advanced CML. The median time from diagnosis to transplant was 2.6 years. Among the MSD BMT recipients, 11 had fully matched marrows and five had advanced CML. The median time from diagnosis to BMT was 0.7 years. All received non-T-depleted marrows after cyclophosphamide and fractionated total-body irradiation. RESULTS Both groups had similar engraftment times. Late graft failure occurred in two URD patients. Graft-versus-host disease (GVHD), &gt; or = grade II, was similar in both groups (77% for URD BMT, 45% for MSD BMT), although more severe acute disease and more persistent chronic disease was seen in the URD group. The Kaplan-Meier estimate of DFS was 45% +/- 15% (SE) and 78% +/- 14% (SE) in the URD and MSD groups, respectively, at 3 years. All had Karnofsky scores of more than 70%, except one URD patient debilitated from GVHD. CONCLUSION CML is eventually fatal to all patients without BMT. The high survival rate seen among children who receive a URD BMT, despite several adverse factors, opens this important therapeutic option to those without an MSD.
P. gingivalis-induced aggregation and ros production in whole blood is dependent on gingipains
Authors: Johanna Lönn, J. Hallström, Torbjörn Bengtsson
Journal: Cardiovascular Research (2012)

A large body of data accumulated over the past several years suggests that the periodontal pathogen Porphyromonas gingivalis is associated with cardiovascular disease. Circulating bacteria may cont ...
Phase I/II study of enzastaurin plus temozolomide during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme (GBM) or gliosarcoma
Authors: N. A. Butowski, K. Lamborn, S. Chang, D. Thornton, R. DeBoer, M. Page, J. Rabbitt, R. Parvanateni, V. Kivett, S. Nicol, M. Prados
Journal: Journal of Clinical Oncology (2007)

12511 Background: Enzastaurin is a potent, selective, oral serine/threonine kinase inhibitor of PKCβ, an enzyme activated by vascular endothelial growth factor (VEGF). VEGF is upregulated in most cases of GBM, producing significant angiogenesis. This study combines the anti-angiogenic properties of enzastaurin with the current standard treatment of radiation therapy (RT) and cytotoxic chemotherapy (temozolomide; TMZ). Methods: A Phase 1/2 study of enzastaurin with TMZ during and following RT is ongoing in patients with newly diagnosed GBM. Two doses of enzastaurin will be evaluated during Phase 1. The first 6 patients will received 250 mg of enzastaurin daily. If no more than one patient experiences a dose-limiting toxicity (DLT) during RT and the first adjuvant cycle, an additional 6 patients will receive an escalated dose of 500 mg daily. The dose established in Phase 1 will be administered to 60 patients in Phase 2. The primary objective of Phase 2 is to determine the efficacy of enzastaurin as measured by overall survival. Multiple pharmacokinetic (PK) and pharmacodynamic (PD) endpoints will be evaluated using perfusion imaging and plasma biomarkers. Relevant growth factors and pathways will be analyzed in primary tumor tissue from each patient. Results: Since September 06, 6 patients have completed RT with concurrent enzastaurin (250 mg) and TMZ. None of these patients has experienced a DLT to date. It is expected that an additional 6 patients will be enrolled in January 07 and Phase 2 will start in May 2007. Conclusions: Enzastaurin with concurrent RT and TMZ appears safe. Final Phase 1 safety results and preliminary PK and PD data will be presented. [Table: see text]
A case of gastric perforation related to sunitinib after radiotherapy of spine in a patient with metastatic renal cell carcinoma.
Authors: S. Richard, C. Dayen, P. Vanelslander, R. Garidi, A. Youssef, M. Bouketouche, Y. Bouguerouche, Y. Douadi, G. Damaj, M. Kanaan
Journal: Journal of Clinical Oncology (2010)

e13141 Background: Sunitinib is a multitarget tyrosine kinase inhibitor with antiangiogenic and antitumoral activities and has been approved for the treatment of advanced renal cell carcinoma. Although the general tolerance is acceptable, serious complications may occur in patients treated with sunitinib. Methods: In a forty-six-year-old man with metastatic renal cell carcinoma who was receiving sunitinib for 12 months, following radiotherapy of painful vertebral metastasis between T3 and L4, a duodenal ulcer perforation resulted with acute peritonitis. Favorable outcome was obtained after surgical intervention. Since there was no therapeutic alternative and also good initial response to sunitinib, the patient continued sunitinib at a lower dose (37.5 mg/d). One year after this episode, the patient presented a fatal upper gastrointestinal bleeding. Results: Two cases of intestinal perforation in renal cancer have been reported in the literature, but no case of gastric perforation. We think that this event was probably due to sunitinib. Several similarities were found in these cases: previous treatment with interleukin 2, a period of treatment with sunitinib more than 12 months, a favorable evolution trend with early management and medico-surgical cooperation. In addition, sunitinib appears to increase radiation-induced cytotoxicity, contributing to the destruction of neo-vessels and tumor control. In our case, the time of occurrence of gastric perforation with the end of radiotherapy was less than six months and the stomach was in the radiation field. However, no cases of intestinal perforation have been described in metastatic breast cancer treated with radiotherapy and bevacizumab, another antiangiogenic molecule. Sunitinib is a multitarget agent and therefore its toxicity profile may have a larger clinical spectrum. Indeed, tyrosine kinase inhibitors have side effects like diarrhea but also of ischemic colitis as these disorders are not reported with bevacizumab. These findings seem to have different pathogenesis poorly understood at present. Conclusions: This is the first published case of gastric perforation associated with sunitinib after irradiation. No significant financial relationships to disclose.
Diet, Nutrition, and Cancer Epigenetics
Authors: Carmen Sapienza, Jean-Pierre Issa
Journal: Annual Review of Nutrition (2016)

The search for a connection between diet and human cancer has a long history in cancer research, as has interest in the mechanisms by which dietary factors might increase or decrease cancer risk. The realization that altering diet can alter the epigenetic state of genes and that these epigenetic alterations might increase or decrease cancer risk is a more modern notion, driven largely by studies in animal models. The connections between diet and epigenetic alterations, on the one hand, and between epigenetic alterations and cancer, on the other, are supported by both observational studies in humans as well as animal models. However, the conclusion that diet is linked directly to epigenetic alterations and that these epigenetic alterations directly increase or decrease the risk of human cancer is much less certain. We suggest that true and measurable effects of diet or dietary supplements on epigenotype and cancer risk are most likely to be observed in longitudinal studies and at the extremes of the intersection of dietary risk factors and human population variability. Careful analysis of such outlier populations is most likely to shed light on the molecular mechanisms by which suspected environmental risk factors drive the process of carcinogenesis.
Evaluation of the value of serum glycomics (GlycoCirrhoTest) for risk prediction of hepatocellular carcinoma in compensated cirrhosis.
Authors: Xavier Verhelst, Dieter Vanderschaeghe, Laurent Castera, Anja Geerts, Nathalie GouttÃƒÂƒÃ‚Â©, Claire Francoz, Francois Durand, Nico Callewaert, Hans Van Vlieberghe
Journal: Journal of Clinical Oncology (2015)

4079 Background: Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC) with a yearly incidence ranging from 1 to 8%. EASL and AASLD guidelines recommend systematic screening with liver ultrasound at 6 months interval in cirrhotic patients. A glycomic based test, called GlycoCirrhoTest, based on to the respective abundance of bisecting GlcNAc residues and triantenarry glycans on serum proteins, has shown a 79% sensitivity and 86% specificity for the diagnosis of cirrhosis among patients with chronic liver diseases. The aim of the present study was to determine whether serum glycomics are predictive for the development of HCC in compensated cirrhotics. Methods: Blood samples of 132 cirrhotic (Child A or B) patients collected between 1995 and 2005 were analysed. Seventy percent suffered of Hepatitis C. In the remaining patients, the cause of cirrhosis was HBV infection, alcohol and autoimmune diseases. Cirrhosis was confirmed by liver biopsy. The patients were followed until the appearance of a HCC, death or liver transplantation. At the moment of serum sampling there was no evidence of HCC. GlycoCirrhoTest was performed using capillary electrophoreses as previously described by Callewaert et al. (Nature Medicine 2004). Results: After a median follow up of 4 years (IQR: 3.6–8.06), 35 (26.5%) of the patients developed a HCC. Mean follow up in the patients who did not develop HCC was 3.7 years (IQR: 3.4-9.9; ns) . There was a significant increase of the mean baseline GlycoCirrhoTest value in the patients who developed a HCC during follow up (p < 0.001) as compared to those who did not. ROC Curve analysis showed an AUC of 0.716 (95% CI: 0.611-0.820) for the prediction of HCC in the patients with a follow up of at least 1 year. An 0.1 increase in the value of the GlycoCirrhoTest was associated with a 27% increase in the risk for developing HCC (OR 1,27; 95%CI: 1,098-1,475). Conclusions: This study suggests that an analysis of the serum protein glycome could generate a useful biomarker for the identification of cirrhotic patients at high risk for the development of HCC. GlycoCirrhoTest may help to stratify cirrhotic patients according to the risk of HCC and optimize screening.
Phase II study of low-dose outpatient chemobiotherapy with temozolomide (TMZ), granulocyte macrophage colony stimulating factor (GM-CSF), Interferon-alpha-2b (IFN), and Interleukin-2 (IL-2) for the treatment of metastatic melanoma
Authors: R. W. Weber, S. O’Day, M. Rose, P. Ames, J. Good, J. Meyer, R. Allen, S. Trautvetter, M. Timmerman, R. Gonzalez, L. E. Spitler
Journal: Journal of Clinical Oncology (2005)

7546 Background: Metastatic melanoma responds poorly to currently available therapies, many of which require hospitalization. de Gast reported that chemobiotherapy with TMZ, GM-CSF, IL-2, and IFN in patients with melanoma has efficacy with toxicity that is manageable on an outpatient basis (de Gast et al Br J CA 88:175–80, 2003). Methods: A multi-centre open-label, Phase II trial of chemobiotherapy in patients with metastatic melanoma has been completed. The treatment regimen consisted of a 28-day cycle in which patients received oral TMZ, 150 or 200 mg/m2 on days 1 - 5, followed by daily outpatient biotherapy on days 6 - 17 with GM-CSF, 125 μg/m2 subcutaneously (SQ), IFN, 5 million units (MU) SQ and IL-2, 4 million international units/ m2 (MIU) SQ. After completion of the biotherapy cycle, patients had an 11-day rest period. The 28-day cycle was repeated as tolerated and clinically indicated. Dose adjustments were made for toxicity depending on the suspected drug interaction. Results: Thirty-one patients (23M, 8F, median age 58) were enrolled in the trial. Of these, 28 (90%) had M1c disease and over half (58%) had 3 or more sites of metastasis. Responses include 4 CR (13%), 4 PR (13%), 7 SD/MR (23%), and 16 PD (52%). The overall objective response rate was 26% (95% confidence interval 12% to 45%); all but 1 of the responding patients had M1c disease. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. The overall survival rate was 52% at 12 months and 25% at 24 months. Five patients (16%) remain alive; 2 patients have no evidence of disease at 34.7 and 25.8 months and 3 patients are alive with disease at 35.3, 28.2, and 23 months. A total of 112 28-day cycles of therapy were administered. Toxicity occurred in 78% of the cycles but was Grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles (thrombocytopenia in 2% and psychosis in 1%). Conclusion: This low-dose chemobiotherapy combination has activity in patients with metastatic melanoma, even in those with M1c disease, is well tolerated, and allows home dosing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron Chiron Chiron
Radiation Therapy With Concomitant Hydroxyurea and Fluorouracil in Stage II and III Head and Neck Cancer
Authors: Daniel J. Haraf, Merrill Kies, Alfred W. Rademaker, Kerstin Stenson, Bharat Mittal, Harold Pelzer, Barry Wenig, Mary Ellyn Witt, Laura Sulzen, Ralph R. Weichselbaum, Everett E. Vokes
Journal: Journal of Clinical Oncology (1999)

PURPOSE: In 1986, a multi-institutional phase II trial was begun to study the use of chemotherapy with concomitant radiation in patients with stage II and III head and neck cancer. End points were overall survival, progression-free survival, local/regional control, and toxicity in the setting of organ preservation with concomitant treatment. METHODS: Eligible patients with stage II or III disease received chemotherapy and radiation on a 2-week cycle. Chemotherapy consisted of continuous infusion fluorouracil (5-FU) at 800 mg/m 2 /d for 5 consecutive days (days 1 to 5) and hydroxyurea (HU) at 1 g orally every 12 hours for 13 doses starting the evening before the start of irradiation. Radiation therapy was given as single 1.8- to 2.0-Gy fractions for 5 consecutive days (days 1 to 5) with chemotherapy. Each 5 days of treatment was followed by a 9-day break (days 6 to 14), during which no additional treatment was given. Treatment cycles were repeated until the completion of the planned radiation dose (six to eight cycles). RESULTS: Between 1989 and 1996, 60 patients were enrolled. All patients were eligible for analysis, with a median follow-up of 52 months for surviving patients and 42 months for all patients. Grade 3 to 4 mucositis occurred in 57% of patients. The 5 year-actuarial overall survival, progression-free survival, and local/regional control were 65%, 82%, and 86%, respectively. Eight patients developed local and/or regional recurrence after treatment. Surgical salvage was possible in three of these patients. Thus, the ultimate 5-year local/regional control was 91%. CONCLUSION: Concomitant radiation and chemotherapy with 5-FU and HU is an effective regimen in patients with stage II and III head and neck cancer. Progression-free survival and local/regional control appear to be superior to expected rates in patients treated with surgery and radiation. Further testing of this regimen in a phase III setting is indicated.
Spirituality, quality of life, and locus of control in a palliative care setting
Authors: P. H. Thaker, C. Sun, D. C. Bodurka, J. Palmer, B. Pei, J. Willey, E. Bruera, L. Ramondetta
Journal: Journal of Clinical Oncology (2006)

18529 Background: A patient’s spirituality/religious beliefs have a profound role on how one copes with disease &amp; on quality of life (QOL). Perceptions of control play an important role in coping not only with stressful experiences, but also in health outcomes. Therefore, the primary objective was to determine whether patients’ spirituality/ religiosity correlates with quality of life and locus of control. Methods: As part of a pilot study, pts presenting for initial outpatient evaluation in the Department of Symptom Control &amp; Palliative Care were enrolled and completed self-report measures: Functional Assessment of Chronic Illness Therapy-General (FACT-G), FACT-Spiritual Well-Being Scale (FACT-Sp), Duke University Religion Index (DUREL), Locus of Control (LOC), Herth Hope Scale (HHS), Predestination (PDQ), and Hospital Anxiety &amp; Depression Scale (HADS). LOC contained 3 subscales: perceived occurrence of chance, dependence on powerful others, and internal control. Pearson correlation coefficients were calculated to explore the relationship between measures. The Mann-Whitney t-test was used to compare patient scores. Results: One hundred patients (48 men &amp; 52 women) completed the surveys &amp; 90% reported a Christian affiliation. QOL was positively correlated with FACT-Sp (p ≤ 0.001, r = .614) and the DUREL which measures both external/internal religiosity (p ≤ .01, r = .291). Interestingly, there was no gender difference in spirituality as measured by FACT-Sp; however, by the DUREL women engaged more frequently in private religious activity when compared with men (p &lt; 0.001). Men had more perceived internal control with less emphasis on the occurrence of chance events or dependence on powerful others on LOC (p = 0.07), as well as a positive correlation with controlling of one’s own fate as measured by the PDQ (p = 0.1). Conclusions: As oncologists committed to providing comprehensive care, we need to be receptive to the spiritual needs of our patients since it augments their QOL and to empower them to have a sense of control. Future studies need to further define these complex relationships and to recognize possible gender differences. No significant financial relationships to disclose.