bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphomas and multiple myeloma in rural Kenya: A cross-sectional survey
Authors: Aluoch J. R. 
Published: March 2020

17558 Background: Prevalence of lymphomas and multiple myeloma in rural referral centers and far isolated district hospitals in Kenya was unknown apart from the teaching hospital, the Kenyatta National Hospital in Nairobi. Methods: A questionnaire on which disease code according to the WHO international diagnostic index (IDIC) numbers was used for data collection for a ten year period from 1991 to 2000. Care was taken to avoid double entry of patients who might have been seen in more than one center. Disease codes were entered for Burkit Lymphoma (BL), Hodgkin’s Lymphoma (HL), Non-Hodgkin’s Lymphoma (NHL), Unclassified Lymphomas and Other Lymphomas (OL) and Multiple Myeloma (MM). Seven rural referral centers, known as Provincial Hospitals (PGH), namely Coast, Nyanza, Western, Central, Eastern, North Eastern and Rift Valley were used for data collection. Results: There were no data from the semi-arid North Eastern province. A total of 1,027 lymphomas were recorded from the six remaining centers. 40.7% were BL, 36% NHL, 12.6% HL and 10.7% UL. There were 133 cases of MM. 87% of BL were from oceano-lacustrine centers. The same applied to 61% of NHL. 43.4% of HL were from Rift Valley, the rest being spread over the other five centers. The same applied to 69% of UL. 81.2% of MM cases were from the high altitude areas of Rift Valley and the mountain region. Conclusions: Although predominance of BL in oceano-lacustrince regions is accouneted for in association with malaria endemicity, we cannot so far account for high prevalence of MM in high altitude regions of Kenya. We also cannot fully account for the absence of any case from the semi-arid North Eastern Province. [Table: see text]
Quality assurance of radiotherapy in the Japan Clinical Oncology Group trial 0211 concerning concurrent chemoradiotherapy for localized nasal NK/T-cell lymphoma: The individual case review
Authors: Oguchi M. , Kagami Y. , Ishikura S. , Nihei K. , Ito Y. , Yamaguchi M. , Tobinai K. , Wasada I. , Hotta T. , Oshimi K. 
Published: March 2020

17561 Background: It is challenging to conduct a high quality multi-institutional clinical trial for localized nasal NK/T-cell lymphoma due to the anatomical complexity and its rarity. The purpose of this study was to evaluate the compliance with protocol guidelines in concurrent chemoradiotherapy for this disease among radiotherapy institutions participating in a multi-center phase I/II JCOG trial 0211. Methods: The treatment consisted of radiotherapy 50 Gy and 3 cycles of DeVIC chemotherapy [carboplatin, etoposide, ifosfamide, dexamethasone] (Yamaguchi M, et al.: Proc ASH, 2005). CT-based three-dimensional treatment planning was required to cover adequately target volumes and to minimize doses to organs at risk such as the eyes, the brain stem and the spinal cord. Patient data were sent to the review center after the treatments have been finalized. The following parameters were evaluated by the quality assurance review board: treatment records and charts; simulation films; portal images; prescribed dose; dose fractionation and overall treatment time; dose distributions; and dose to risk organs. Results: At the time of phase I analysis, 10 patients were enrolled in this study. In 2 of 10 cases, process of treatment planning was not available. There was no protocol violation. Major deviations were identified as follows: Delineation of clinical target volume (< 2 cm from the edge of the gross tumor volume at any direction), 2/10; dose distribution (not covered by 90%-115% isodose line), 1/10; and dose to optic chiasm (>40 Gy), 1/10. All cases were compliant in prescribed dose, dose fractionation, and overall treatment time. In the last 4 of 10 cases, attending radiation oncologists at the participating institutions were contacted by the radiation oncology study chair and they discussed the treatment planning just after patient enrollment. These 4 cases were all protocol compliant compared to 6 cases with 4 major deviations. Conclusions: Individual case review is essential in a multi-center clinical trial to keep enrolled cases protocol compliant and minimize inter-institutional variations. We expect that our quality assurance program will maintain the quality of the JCOG trial 0211. No significant financial relationships to disclose.
Development of CMRF-56 blood dendritic cell preparations for immunotherapy of multiple myeloma
Authors: Vari F. , Rossetti T. , Munster D. , Hart D. 
Published: March 2020

17572 Background: Despite advances in therapy for multiple myeloma, such as the use of proteosome inhibitors or stem cell transplantation, it is usually incurable. One promising therapeutic approach is to eradicate residual disease after stem cell transplantation by immune therapy. Method: The CMRF-56 monoclonal antibody detects an antigen expressed on blood dendritic cells (BDC) that is expressed after a short in vitro culture period. With clinical trail applications in mind, we have developed a procedure for isolation of CMRF-56+ BDC using CliniMACS. Cell culture, antibody staining and immunoselection occur in a closed system, compatible with regulatory requirements for cell therapy. Simultaneously, our team has developed of a bioprocess for production of the murine biotinylated CMRF-56 antibody for clinical trials. The bioprocess incorporates components that remove contaminating DNA, host cell proteins, viral particles and endotoxin. Results: Positive immunoselection using this antibody produces a BDC population containing some contaminating CMRF-56 positive B cells and monocytes. CliniMACS selection of PBMC from an apheresis produces enough BDC for a vaccination program with an average recovery of 1%, purity of 38%, yield of 48% and viability of 70%. These CMRF-56 dendritic cell preparations have been used to generate strong T cell responses to influenza matrix peptide and the putative tumour antigen MART-1. In order to discover and validate additional antigens capable of inducing effective immune responses against multiple myeloma, we have tested numerous of potential target antigens. It has been possibe to generate moderate specific immune responses against HM1.24 and mucin 1 peptides in normal HLA A2 donors. Using the CMRF-56 dendritic cell preparation as antigen presenting cells, it is possible to generate strong cytotoxic T cell responses against a lysate of the myeloma cell line U266. Indicating the potential usefulness of a whole cell lysate in generating anti-myeloma T cells for immunotherapy. Conclusions: These studies have provided the necessary pre-clinical data to commence a Phase I Clinical Trial in 2006 using CMRF-56 BDC preparations loaded with myeloma and control antigens in myeloma patients with minimal residual disease. No significant financial relationships to disclose.
Four years trial in elderly people of appraisal and comparison by geriatric assessment instruments: Use of high potency opioids for cancer pain control and quality of life
Authors: Ferrero G. , Testore F. , Milanese S. , Porcile G. , Caroti C. , D’Amico M. , Folco U. , Gozza A. 
Published: March 2020

18610 Background: Pain is probably under-recognized and under-treated in the Elderly with advanced cancer disease but the effect of a therapy with high potency opioids is not studied so much in geriatric age people. To evaluate efficacy and tollerability of escalating doses of Transdermal Fentanyl (TTS-F) or equipollent doses of oral morphine long acting with Immediate Release Oral Morphine (IROM) as rescue medication for treatment of moderate-severe cancer pain, we have started a Multicentric Observational Analysis in four cancer centres of north-western Italy. Studies of oncological palliation using valid measures of quality of life show that patients may be willing to accept some side effects of treatment as long as they gain relief from tumor-related symptoms Methods: -TIQ (Therapy Impact Questionnaire) -VAS (Visual Analogic Scale): 0 to 10 -Toxicity (WHO criteria) -Geriatric Assessment for pts aged >70 yrs (only at time 0): CIRS (Comorbility Index) IADL/ADL (Instrumental Activities Daily Living/Activities Daily Living). Patients characteristics -159 pts -Total Median Age: 66 yrs (range 38–86) -Median ECOG PS: 1 (range 0–2) -Elderly (>70 yrs): 75. Pain Starting situation -Median starting VAS: 5.5 (range 3–9) -TIQ: depression 70 pts, cachexia 55 pts, dispnoea 40 pts -CIRS (Comorbidity index): comorbidity were present among 66 pts. TTS-Fentanyl starting dose: 25 mcg/h every 72 h (range 25–50 mcg) or oral morphine long acting 60–90 mg plus IROM 10 mg every 4–6 hours for breakthrough pain present in 38 pts Results: -Quickly pain VAS downloading during first two weeks of treatment (median VAS 1) -Analgesic doses were not significantly increased after two months and not exceeded WHO grade 2 -IROM rescue was similar to that observed for the overall population -TIQ, ADL and IADL were not influenced by therapy. Conclusions: High potency opioids (TTS-F or long acting morphine equipollent doses, plus Rescue-IROM) offers durable long term maintenance pain relief wild acceptable toxicity also in elderly people, is particularly useful for cancer pts with compliance problems and may be considered as first-line treatment for moderate/severe cancer pain. No significant financial relationships to disclose.
Coping and survival in breast cancer patients evaluated in a 5-year follow-up
Authors: Andritsch E. , Dietmaier G. , Hofmann G. , Ladinek V. , Zloklikovits S. , Petru E. , Samonigg H. 
Published: March 2020

18624 Background: A notable amount of studies investigated possible relations between the kind of coping with the disease and the survival in cancer patients. There is some evidence that distress is a predictor of shortened survival and that active coping is related to better chances. Nevertheless many of those studies were limited by small sample sizes or a retrospective design and the published data are inconsistent. Methods: This investigation of 212 breast cancer patients (stage I and II) in an adjuvant, disease free situation started 5 years ago about 3 years after the initial diagnoses and was carried out at three different measuring times (5 and 4 years ago and at present). It was an attempt to explore whether the preferred coping styles implicate survival. Results: At present 3.8% (N = 8) of the patients have died because of their cancer and 10.8% (N = 23) are suffering from a relapse. Significant relations between recurrence and avoidance (F1;178 = 3.973; p = 0.048) measured with the IES (Impact of Event Scale) five years ago and between recurrence and avoidance (F1;164 = 6.788; p = 0.010) and aggression (F1;164 = 3.277; p = 0.038) measured with the BSI (Brief Symptom Inventory) four years ago were found with MANOVAs. Patients, who stated a higher level of avoidance and aggression, were at higher risk to become a relapse or metastases. Patients having a progressive course of disease tended to be younger (57.2 years) than patients being free of disease (61.3 years, F1;179 = 3.294; p = 0.070). Regarding the 8 year survival those patients, who had died, stated a higher level of anxious preoccupation measured with the MAC (Mental Adjustment to Cancer Scale) 5 years ago (M-W-U = 397.5; p = 0.48). Conclusions: The results of this study provide an essential aspect for psychological support and of the necessity to include psychooncological elements in physician-patient-communication. No significant financial relationships to disclose.
Competency building for self-management and self-care: evidence informed development of an empowerment course for breast cancer survivors
Authors: Nyhof-Young J. , Regehr M. , Secord S. , Jusko Friedman A. , Catton P. 
Published: March 2020

18626 Purpose: To improve survivorship outcomes by empowering and preparing survivors to self- manage their health. We describe the evidence-informed development of a patient empowerment course “Managing Your Cancer Journey” offered in the Breast Cancer Survivorship Program at Princess Margaret Hospital in Toronto, Canada. Methods: Audio-taped and transcribed focus groups (3; n = 16 patients, August 2004), interviews (n = 8 lymphedema patients, spring 2004, n = 8 patients, spring 2005) were held for patient directed guidance in survivorship course and program development. A comprehensive literature review was conducted to develop a theoretical framework for empowerment. Three main competencies: knowing, navigating and negotiating emerged and were developed into 5 ×1.5 hour classes facilitated by two social workers in collaboration with health professionals and community organizations. Feedback from survivors in a community forum (n = 40) and during piloting with survivors (n = 10) and educators was solicited. Analysis of transcripts and observer/consultant debriefings were analyzed for emergent themes. Results: Respondents recommended program interventions that allowed people to gain mastery or a perceived sense of control over their lives with cancer. Survivors and expert consultants prioritized 3 major domains for the survivorship program: psychosocial support, information provision, and support for dealing with the physical effects of breast cancer. In response, outcome measures for empowerment will include: patient satisfaction, cancer knowledge, self-efficacy in disease management, empowerment, and depression. Conclusions: Ongoing iterative feedback from and piloting with the survivor target audience and embedding the course within the hospital’s strategic plan for patient centred care and competency building are keys to successful course implementation. No significant financial relationships to disclose.
Survival of patients with soft tissue sarcoma (STS) correlated to tumor grade, size, site of origin & cell type. Does the high risk group need adjuvant systemic therapy?
Authors: Elias E. G. , Brown S. D. , Dorsi O. K. , You C. J. , Nitz A. M. 
Published: March 2020

19510 Background: The prognosis of patients with STS depends on the tumor stage, which includes tumor size (T) and grade (G). Patients with low-grade tumors (G1) are managed by radical resection only. Patients with moderate (G2) and high-grade (G3) tumors require postoperative adjuvant radiation therapy (RT); this became standard therapy. This study was conducted to determine the efficacy of standard therapy on survival. Methods: This is a retrospective study of patients with primary STS, excluding those with skin, subcutaneous tissue and GIST. All patients underwent radical resections (S). Postoperative RT was requested for G2 and G3 tumors; 6 patients with G3 tumors received chemotherapy (C) prior to RT. Results: 52 patients were studied with a median follow-up of 84 mo. The overall survival ranged from 3 to 264 mo. with a median of 52 mo. The incidence of tumor grade and size were correlated to the survival. 37 patients had STS of the extremities and torso; 24 are alive. 10 patients had intra- and retro-peritoneal STS; 5 are alive. 4 of the 6 patients who received C are alive, 3 are disease-free for a period of 3 to 7 years. Life table analysis of patients with G3T2 tumors comparing the 3 treatment groups (S vs. S+RT vs. S+C+RT) showed no statistical difference in survival, but there was a trend in favor of S+C+RT. Conclusions: 1. Radical resection and postoperative RT may be insufficient for systemic control. 2. Adjuvant systemic chemotherapy may improve the survival, and may be safer than RT in the management of retroperitoneal and visceral sarcomas. [Table: see text] No significant financial relationships to disclose.
Phase I study to determine tolerability and pharmacokinetics (PK) of SB-743921, a novel kinesin spindle protein (KSP) inhibitor
Authors: Holen K. D. , Belani C. P. , Wilding G. , Ramalingam S. , Heideman J. L. , Ramanathan R. K. , Bowen C. J. , Williams D. D. , Hodge J. P. , Dar M. M. 
Published: March 2020

2000 Background: SB-743921, a potent and selective inhibitor of KSP (Ki =100 pM; >40,000-fold selectivity vs other kinesins), causes mitotic arrest, potent inhibition of tumor cell proliferation, and demonstrates activity in a broad range of human tumor xenografts. Methods: A phase I study was conducted to determine the maximum tolerated dose (MTD) and PK profile of SB-743921 when administered IV over 60 minutes every 21 (Q 21) days (d). Results: 44 patients (pts) (M/F 19/25), median age 61.5 yrs (range 32–80, with solid tumors were treated at doses of 2 (n=2), 4 (n=27), 5 (n=6), 6 (n=3), and 8 (n=6) mg/m2 (median cycles 2, range 1–10, total cycles 101). Frequent tumor types included colorectal (n=11), ovarian (n=5), NSCLC (n=5), esophageal (n=4), and pancreatic (n=4). Dose-limiting toxicities (DLTs) at 8 mg/m2 consisted of (max CTC grade/pt) prolonged grade (gr) 4 neutropenia (n=2), gr 3 elevated ALT/AST (n=1), and gr 3 elevated bilirubin (n=1). DLTs at 6 mg/m2 were gr 3 hyponatremia (n=1) and prolonged gr 4 neutropenia (n=1). DLTs at 5 mg/m2 were limited to febrile neutropenia (n=2). The 4 mg/m2 dose level was determined as the phase II dose. Toxicities at 4 mg/m2 included gr 1 fatigue (n=8) and neutropenia [gr 1 (n=4), gr 2 (n=7), gr 3 (n=3), gr 4 (n=2)]. Neutropenia nadir was day 6–8 with recovery to gr ≤2 by day 15. Gr 3 non-hematologic toxicities at 4 mg/m2 included gr 3 ALT (n=1), gr 3 AST (n=2), gr 3 hyperbilirubinemia (n=1), gr 3 hypophosphatemia (n=1), and gr 3 alkaline phosphatase elevation (n=1). Median PK values in cycle 1 at 4 mg/m2 were: Cmax 473 ng/ml, AUC0-∞ 5207 ng.hr/ml, and t½ 36 hr. AUC0-∞ and Cmax were proportional to dose. No consistent correlation was observed between DLTs and PK parameters. Stable disease for ≥ 4 cycles (range 4–11) was observed in 6 pts (4 pts at 4 mg/m2; 1 pt at 6 mg/m2; 1 pt at 8 mg/m2). A pt with cholangiocarcinoma had evidence of radiographic tumor regression (post cycle 10) and a >50% decrease in her CA 19–9. Conclusions: The recommended phase II dose of SB-743921 on the Q 21 day schedule is 4 mg/m2. The observed toxicities at the recommended phase II dose are manageable and reversible. The onset and duration of neutropenia is predictable. [Table: see text]
Screening a library of FDA-approved drugs identifies agents that induce lytic viral infection in EBV-associated tumors
Authors: Chen J. , Chong C. , Hsieh W. , Fu D. , Lemas V. , Liu J. O. , Ambinder R. F. 
Published: March 2020

2002 Background: Epstein-Barr virus (EBV) is associated with a variety of tumors including AIDS lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma and Hodgkin’s lymphoma. We hypothesized that drugs used in practice might alter viral gene expression in tumor cells in ways that might be important to understand. For example induction of lytic viral gene expression leads to expression of immunodominant CD8 T cell antigens and expression of the viral thymidine kinase (which phosphorylates ganciclovir and other nucleotide analogues). Methods: A library of FDA-approved drugs that includes 2720 agents was screened to identify those that upregulated EBV lytic gene expression. The screen involved a Burkitt’s cell line with a recombinant GFP-EBV that assayed the impact of agents on replication of the complete viral genome, and assay of a lytic promoter reporter construct. Results: The assay identified 146 agents in the whole virus replication assay, 195 agents in the promoter assay, and 54 agents that were active in both assays. Agents with activity could be grouped into 4 families: anti-tubulin drugs, glucocorticoid and other steroid hormones, DNA damaging agents and nucleotide analogues (including cytarabine and gemcitabine), and the proteasome inhibitor bortezomib. Anti-tubulin drugs and nucleotide analogues were less active in thes whole virus assay than the promoter assay whereas bortezomib showed similar activity in both assays. Followup studies confirmed that bortezomib is a potent viral lytic activator that increases expression of the viral thymidine kinase and virion production in several different Burkitt’s lymphoma and primary effusion lymphoma cell lines. Although bortezomib decreases NFKB levels, in vitro investigations with an IKB repressor suggests that inhibition of NFKB alone does not account for lytic activation. Conclusions: Many cancer chemotherapeutic agents are upregulators of EBV lytic expression. Bortezomib is among the most potent. As strategies for using lytic induction therapeutically evolve, these agents may have an important role to play. No significant financial relationships to disclose.
Wavelet-based prognostic model with comparative genomic hybridization (CGH) data in patients with hepatocellular carcinoma (HCC)
Authors: Zee B. C. , Lee J. , Wong N. , Yeo W. , Lai P. , Chan L. , Hui P. , Wong H. , Lam K. , Ho W. , Chan A. T. 
Published: March 2020

20026 Background: In order to obtain a good prognostic model for HCC, clinical data alone may not be adequate. DNA microarray technology has enabled quantification of thousands of genes in a single assay but it has the inborn drawback of high background noise. In order to deal with the problem of information overflow, we developed multivariate dependencies approach using CGH to guide the initial modeling process. This approach takes into account the multivariate nature and potential interaction among the genes during the prognostic modeling process. Methods: The study includes 165 patients with CGH data containing 858 regions/bands. The clinical outcome is survival at 1.72 years. Potential prognostic factors include CGH regions, albumin, ALT, bilirubin, AFP, ascites, alkaline phosphatase (ALP), tumor size, and encephalopathy. We used a blocked wavelet-shrinkage principal component analysis (BWSPCA) to reduce the dimension of CGH data with respect to clinical outcome and followed by logistic regression. We compared the BWSPCA with PCA alone, supervised PCA (Bair et al. 2004), and supervised BWSPCA. Results: Among the 165 patients, 133 (80%) were male, average age of 54.8 years, 78 (47%) stage I-II and 75 (45%) ECOG 0–2. PCA alone and supervised PCA models failed to identify significant CGH regions. BWSPCA model includes tumor size (p = 0.005), albumin (p = 0.047), ALP (p = 0.025), Chr.6q25.1 (p = 0.031), Chr.12q24.32 (p = 0.012), Chr.Xq28 (p = 0.035). Supervised BWSPCA approach includes tumor size (p = 0.016), ALP (p = 0.002), Chr.12q24.11 (p = 0.047). The area under the receiver operating curve (ROC) for the BWSPCA model was 0.78 with a sensitivity and specificity about 0.8 and 0.6 respectively. Conclusions: PCA alone is not effective in identifying CGH regions as prognostic factors. Supervised learning approach did not improve the results. The BWSPCA method identified a number of significant CGH regions associated with survival outcome for HCC patients. These results would be verified in future study. This method will be extended and applied to develop prognostic models using both CGH and DNA microarray data. Acknowledgement: This study is funded by the Research Grant Council of Hong Kong #CUHK4469/03M. No significant financial relationships to disclose.