bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibiting TNFα with etanercept in relapsed/refractory follicular lymphoma
Authors: Jacobsen E. , Van Den Abbeele A. D. , Neuberg D. , Li S. , Fisher D. C. , Friedberg J. , Barnes A. S. , Yap J. T. , Kutok J. , Freedman A. S. 
Published: March 2020

17525 Background: Follicular dendritic cells (FDC) support the survival of follicular lymphoma (FL). TNFα is overexpressed by FL cells and TNFα plays a central role in the development and maintenance of normal FDCs. TNFα may be an ideal target for therapy due to its pleotropic effects on FDCs. Inhibition of TNFα is possible with the decoy receptor, etanercept. Methods: Patients with relapsed/refractory FL received 8 weeks of etanercept, 25 mg SC on day 1 and 4 of each week. Patients with any response or stable disease (SD) received 16 more weeks of etanercept at the same dose/schedule. 7 patients enrolled from April 2002 to September 2005. Median age was 63. All patients had stage III/IV disease and had received multiple chemotherapy regimens (median 3); 2 had prior autologous stem cell transplant. FDG-PET was performed at baseline and after 8 (scan 1, n = 7 patients) and 24 weeks on therapy (scan 2, n = 3 patients). Maximum standardized uptake values (SUVmax) were measured in up to 3 lesions per patient (n = 17 lesions for scan 1; 7 lesions for scan 2). The summation SUVmax of all lesions was calculated at each time point. The percentage (%) change in SUVmax in individual lesions and the summed SUVmax for each patient was calculated relative to baseline. The % metabolic response (mR) was assessed using EORTC thresholds for % SUVmax change (mPR ≤ −25% < mSD < +25% ≤ PD). Results: All patients completed at least 8 weeks of etanercept. 2 patients completed 24 weeks. 5 patients had minor or mixed responses. At the 8 week evaluation 5 patients had SD and 2 had progressive disease (PD). Of the 5 with SD, 2 progressed at 9 and 12 weeks of therapy and 3 progressed by 24 weeks. PET scan 1 showed mPR in 5/7 pts, SD in 2/7 and no PD. PET scan 2 showed mPR in 2/3 pts, mSD in 1/3 and no mPD.All patients are alive at a median of 20+ months after therapy. 1 grade 3 toxicity (lymphopenia) and 3 grade 1/2 toxicities (rhinitis/URI and 2 injection site reactions) were reported. Conclusions: Etanercept was well tolerated and minor clinical responses were observed. By EORTC criteria for metabolic response, mPR occurred in 5/7 pts, mSD in 2/7 and there was no mPD. The significant number of metabolic PR’s suggest that targeting the microenvironment with agents like etanercept may be a novel treatment approach for FL. No significant financial relationships to disclose.
Ten year retrospective analysis of BOP (bleomycin, vincristine, predinisone)—A novel non-myelosuppressive chemotherapy regimen for treatment of non-Hodgkin’s lymphoma
Authors: Chan A. , Nay D. , Hopman W. , Galbraith P. , Baetz T. 
Published: March 2020

17560 Background: Non-Hodgkin’s Lymphoma (NHL) represents the most common hematological malignancy in North America. Patients with advanced NHL, particularly those with pancytopenia, often do not tolerate the myelosuppressive side effects of chemotherapy. BOP (Bleomycin 10 mg/m2 IV D1, Vincristine 1.4 mg/m2 (max 2 mg) D1 and Prednisone 100 mg PO on D1,3,5,) q weekly ± Rituximab 375 mg/m2 IV D1 has been used as a non-myelosuppressive chemotherapy regimen for patients with advanced NHL at the Cancer Centre of Southeastern Ontario (CCSEO). Methods: This was a retrospective chart review of patients with NHL who have been treated with ≥1 cycle of BOP ± R at the CCSEO in the last 10 years. Primary endpoints included an assessment of patient demographics, clinical setting, clinical response, survival and toxicity. Results: Eighty-two patients were treated with BOP ± R (71 BOP, 11 R-BOP). The patient population was 59% male and 80% stage ≥3. The most common histology was Diffuse Large B cell Lymphoma (22%) and Follicular Lymphoma (19.5%). Eighty percent of patients had an IPI score ≥2. The median number of chemotherapy treatments prior to BOP was 2. Overall, the response rate (CR + PR) was 46.3% with a mean duration of response of 4.6 months. Median survival was 3.8 years. BOP was used successfully as a salvage regimen prior to stem cell transplant in three patients and as a first line treatment prior to myelosuppressive treatment in 19 patients. The regimen was generally well tolerated with no hematologic toxicity or infectious complication. Four patients experienced mild pulmonary toxicity. There were no deaths attributable to drug toxicity. Response rates and toxicities in the R-BOP population were not significantly different from those of BOP. Conclusions: Patients with advanced poor prognosis NHL have a favorable response rate associated with minimal toxicity to the non-myelosuppressive chemotherapy regimen BOP ± R. No significant financial relationships to disclose.
Preliminary results from two phase II studies of lenalidomide monotherapy in relapsed/refractory non-Hodgkin’s Lymphoma
Authors: Wiernik P. H. , Lossos I. S. , Justice G. , Zeldis J. B. , Takeshita K. , Pietronigro D. , Habermann T. M. , Witzig T. E. 
Published: March 2020

17569 Background: Lenalidomide is an immunomodulatory drug of the IMiD class that has activity in multiple myeloma, myelodysplastic syndromes and chronic lymphocytic leukemia. We report preliminary results of two Phase II studies assessing the safety and efficacy of lenalidomide monotherapy in subjects with relapsed/refractory indolent or aggressive non-Hodgkin’s lymphoma (NHL). Methods: Subjects with indolent (study NHL-001) or aggressive (study NHL-002) relapsed/refractory NHL following ≥ 1 prior treatment regimen with measurable disease are eligible. Subjects receive 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continue therapy for 52 weeks as tolerated until disease progression. Response and progression are evaluated using cross sectional imaging by the NCI criteria. Results: 10 subjects (2 indolent (I), 8 aggressive (A)) of a planned 80 (40 in each study) have enrolled thus far. Median age is 66 (45–80) and 7 subjects are female. Indolent histology is follicular center lymphoma grade 1, 2 (n = 2) and aggressive histology diffuse large cell lymphoma (n = 7) and follicular center lymphoma grade 3 (n = 1). Median time from diagnosis to lenalidomide monotherapy is 2.9 years (1.1–10) and median number of prior treatment regimens per subject is 3 (1–6). Median duration of follow-up is 2 months. Of eight subjects (2 I, 6 A) evaluable for response at two months, three demonstrated a decrease in their tumor burden by 72% (I), 68% (A) and 52% (A), two subjects (2 A) exhibited stable disease and three subjects (1 I, 2 A) had disease progression. Six of the ten subjects (2 I, 4 A) demonstrated no Grade 3 or 4 adverse events. Grade 3 or 4 hematological adverse events (neutropenia, thrombocytopenia) occurred in four subjects including one febrile neutropenia and one of these four subjects also exhibited Grade 3 cellulitis. No tumor flare or tumor lysis has been observed to date. Conclusions: Preliminary data of lenalidomide monotherapy in relapsed and refractory NHL are encouraging. [Table: see text]
RAD001 (everolimus) down-regulates cyclin D3 and c-Myc and is particularly effective in the treatment of aggressive B-cell lymphomas
Authors: Kuo S. H. , Hsu C. H. , Yeh P. Y. , Hsu H. C. , Gao M. , Cheng H. J. , Cheng A. 
Published: March 2020

17573 Background: Aggressive B-cell lymphoma is recently found to be associated with constitutive activation of the PI3K/Akt pathway, and thereby is relatively resistant to apoptosis. Furthermore, activation of the PI3K/Akt signaling pathway can result in the upregulation of cyclin D3 and c-Myc through inhibition of the cap-independent RNA translation. Since mTOR is closely associated with the regulation of the translation process, and is a downstream mediator of the PI3K/Akt signalling pathway, this study aimed to examine if RAD001, an inhibitor of mTOR, can be effective in the treatment of aggressive B-cell lymphoma. Methods: Pfeiffer (diffuse large cell lymphoma), Ramos (EBV (−) Burkitt’s lymphoma), Raji (EBV (+) Burkitt’s lymphoma), and MC116 (EBV (−) undifferentiated lymphoma) cell lines were used in this study. Expression of pAkt, p70S6 kinase, pp70 S6 kinase, 4E-BP1, p4E-BP1, cyclin D3, and c-Myc was measured by immunoblotting. Results: Akt was constitutively activated in all four lymphoma cell lines. Downstream effectors of PI3/Akt signaling pathway, including p70S6 kinase and 4E-BP1, were also phosphorylated in these lymphoma cell lines. RAD001 downregulated p70S6 kinase and 4E-BP1, and the IC50s of growth suppression ranged from 5 to 50 nM, without significant difference between EBV (+) and EBV (−) cell lines. The IC50s of these lymphoma cell lines appeared to be much lower than those obtained from the carcinoma cell lines, suggesting that lymphomas may be particularly sensitive to growth inhibition by RAD001. RAD001 blocked cell cycle progression in G0/G1 phase in all four lymphoma cell lines while there was no significant increase in sub-G1 phases, suggesting that apoptosis was not the major mechanism of RAD001-induced growth inhibition. In addition, in parallel with the RAD001-induced growth inhibition, a dose-dependent down-regulation of the expression of cyclin D3 and c-Myc was demonstrated. Conclusions: The mechanism of action is at least partly due to downregulation of cyclin D3 and c-Myc, and subsequent G0/G1 block. Since overexpression of cyclin D3 and c-Myc is also closely associated with chemoresistance of aggressive B-cell lymphoma, RAD001 may be a useful adjunct in the treatment of this group of tumors. No significant financial relationships to disclose.
The fears of men in a prostate cancer support group: A pilot study
Authors: Hausdorff J. 
Published: March 2020

18616 Background: Little is published on prostate cancer patients’ fears and the effectiveness of interventional strategies. Methods: A 20-item questionnaire addressing various potential fears was administered to 30 men in a local prostate cancer support group: 15 had undergone curative therapy and were NED, and 15 had recurrent disease on androgen suppression. Level of fear for each question was rated from 1 to 5. At a later date, a different questionnaire was administered to 10 men with recurrent disease, addressing the predominant fear previously identified—uncontrolled symptoms at the end of life—with 10 specific questions on this subject. This was followed by the intervention: a 90 minute group discussion, led by an MD boarded in Medical Oncology and Hospice and Palliative Medicine. To assess impact, the 10 item questionnaire on end of life symptoms was readministered immediately after the discussion, and again 2 months later. Results: a) Patients with recurrent disease expressed a greater degree of fear than those free of recurrence; b) A major fear of the future is of uncontrollable symptoms at end of life, and was more of a concern than death itself; c) Of the 7 (of 10 total) items that were most significant to the patients (mean score 2.9 or higher, scale 1–5), a mean drop of 0.7 was seen in the level of fear following the intervention; d) This was inconsistently sustained 2 months later, with some concerns lessened but others not. Conclusions: In this small pilot study of men with prostate cancer, there appeared to be some measurable impact on the level of fear following the group discussion, though inconsistently sustained; questionnaires such as this are feasible to administer and appear to encourage productive discussion of difficult issues in the support group setting. No significant financial relationships to disclose.
Bisphosphonates and oral cavity avascular bone necrosis: A review of 12 cases
Authors: Salesi N. , Pistilli R. , Marcelli V. , Govoni F. A. , Di Cocco B. , Pacetti U. , Di Fonso C. , Ciorra A. , Natali M. , Veltri E. 
Published: March 2020

18628 Background: Intravenous bisphosphonates are the current standard of care for the treatment of hypercalcemia of malignancy and for the prevention of skeletal complications associated with bone metastases. Generally, the i.v. administration of bisphosphonates is well tolerated. Recently, retrospective case studies have reported an association between long-term bisphosphonate therapy and osteonecrosis of the jaws. Methods: We reviewed data for 12 patients referred to either an oral and maxillofacial surgeon or an oral medicine specialist for the management of clinically apparent chronic oral osteonecrosis of unknown etiology. All had received therapy cancer-related simultaneously with bisphosphonate management. Results: Typical presenting symptoms were pain and exposed bone at the site of a previous tooth extraction. In most patients, lesions initially occurred after dental extraction or other odontostomatological procedures, and 5 had a spontaneous event. Biopsy of the involved area showed the presence of necrotic lacunae, with infiltration of lymphocytes and histiocytes. In 9 cases, histological or cytological diagnosis of suspicious osteomyelitis was done. There was no observed correlation of the intraoral lesions with myelosuppression secondary to antineoplastic therapy. Conclusions: Based on these patients’ respective histories, clinical presentations, and responses to surgical and antibiotic treatments, it appears that the pathogenesis of this osteonecrotic process is most consistent with localized vascular insufficiency. In our opinion, the mechanism by which bisphosphonates could compromise bone vascularity may be related to its effect on the osteoclasts. The potent bisphosphonate mediated inhibition of osteoclast function serves to decrease bone resorption and inhibit normal bone turnover remodeling, resulting in microdamage accumulation and a reduction in some mechanical properties of bone. No significant financial relationships to disclose.
Quality of life in children with osteosarcoma after limb salvage operation
Authors: Aono M. , Kudawara I. , Ohzono K. , Aoki Y. , Matsumine A. , Ieguchi M. 
Published: March 2020

19501 Background: There are several options for the surgical management of osteosarcoma (OS) especially in the skeletally immature patients. We evaluate the clinical results and quality of life (QOL) of OS patients with limb salvage operations. Methods: From 1996 to 2005, ten children with newly diagnosed previously untreated nonmetastatic (stage IIB) OS of extremities were reviewed. There were 5 females and 5 males. The median age was 12 years (range, 8 to 14). Tumor locations: proximal humerus in 2, proximal femur in 1, distal femur in 2, proximal tibia in 3, distal tibia in 1, and tibial shaft in 1. Patients received neoadjuvant and adjuvant chemotherapy, and local wide resection of tumor. Limb salvage procedures: intraoperative extracorporeal autogenous irradiated bone graft (IORBG) in 4 and prosthetic replacement in 6. The functional results were measured for the patients accordance with the Musculoskeletal Tumor Society rating score. Results: With a median follow up of 4 years (range, 1 to 9), 7 were continuously disease free, 2 died of disease and in one there was no evidence of disease. No local recurrence was seen. Mean functional rating scores of patients with IORBG and prosthetic replacement were 82% (range 77 to 90) and 82% (range 57 to 93), respectively. Functional results were not different between these study groups and relatively good. There was one infection in patients with prosthetic replacement. There were subchondral collapse in 2 (50%), fracture in 1 (25%) and infection in 1 (25%) with IORBG. Conclusions: Limb salvage operation with neoadjuvant chemotherapy is the optimum treatment. However there remain several problems of function after limb salvage operations, with improvement of survival of pediatric osteosarcoma patient. We should select the most suitable surgical procedure to achieve the good function of limbs as well as local control. No significant financial relationships to disclose.
Dramatic response of metastatic peripheral nerve sheath sarcoma to cetuximab combined with doxorubicin-based chemotherapy: Report of a case
Authors: Holmes J. P. , Reid T. J. 
Published: March 2020

19503 Background: Soft tissue sarcomas are aggressive tumors that often show poor response to conventional chemotherapy agents. Some of these tumors over express epidermal growth factor receptor (EGFR) which is thought to promote tumor growth. Cetuximab, a monoclonal antibody to EGFR, is FDA approved for use in colon cancer. We report a case here of use in a patient with an aggressive soft tissue sarcoma. Case Report: A 32 yr male presented in April 2005 for routine follow up three months after completing adjuvant radiotherapy for retroperitoneal soft tissue sarcoma. At this time the patient was found to have recurrence of disease on routine surveillance scans. During workup of the recurrent masses, he developed acute bowel obstruction and went emergently to the OR. Multiple masses were removed and he was rendered grossly disease free. Adjuvant adriamycin and ifosfamide were planned; however, bulky masses were again noted on a pre-chemo staging study. After a single cycle of chemotherapy, he presented with abdominal pain, and an urgent CT scan ordered showed progressive disease. Immunohistochemical stains demonstrated strong expression of EGFR on his tumor. Cetuximab was added to his chemotherapy regimen. Repeat studies showed dramatic (>30%) decrease in his tumor burden after only two doses. As cycle three began, the patient developed acute abdominal pain and fever; emergent scans showed free air within the abdomen. The majority of his tumor burden had continued to decrease. The perforation could not be surgically managed and the patient was discharged to hospice. He expired ten days after discovery of the perforation. Conclusions: Addition of cetuximab to therapy for an aggressive soft tissue sarcoma which overexpressed EGFR resulted in dramatic decrease in tumor burden. Unfortunately, the patient suffered perforation of abdominal viscera and subsequently expired. Rapid tumor shrinkage likely contributed to the perforation. Use of cetuximab in patients with aggressive tumors expressing EGFR should be explored in the setting of clinical trials. No significant financial relationships to disclose.
Prognostic significance of disseminated cancer cells in bone marrow in patients with squamous cell carcinoma of the esophagus using quantitative RT-PCR for CEA mRNA
Authors: Shinjo K. , Kajiyama Y. , Ishii Y. T. , Nagaoka I. , Tsurumaru M. 
Published: March 2020

20004 Background: The clinical significance of disseminated cancer cells in bone marrow has not been elucidated in esophageal cancer. The aim of this study was to evaluate the relation between quantity of disseminated cancer cells in bone marrow and clinical characteristics, including prognostic significance, in patients with squamous cell carcinoma of the esophagus using real time reverse transcriptase polymerase chain reaction (RT-PCR) for CEA (carcinoembryonic antigens) mRNA. Methods: Bone marrow samples were obtained from the 4th or 5th right rib on thoracotomy from consecutive 65 operative patients with esophageal squamous cell cancer, who received esophagectomy with lymph node dissection. After total RNA extraction, they were investigated by quantitative real time RT-PCR for CEA. We also performed qualitative analyses to confirm the results at least twice. We adopted quantitative results when qualitative analyses showed positive. Results: In bone marrow CEA mRNA was detected in 14 out of the 65 patients (21.5%). There were no significant differences in clinicopathological findings between positive and negative group for bone marrow CEA. However, after a short median follow-up of 12 months (3–19 months), 6 of 14 (42.9%) patients with positive CEA group had been dead compared to 4 out of 51 (7.8%) patients with negative CEA group. The survival time of both group showed a significant difference (p=0.0282). However, there was no relationship between the amount of cancer cells in bone marrow and patients’ survival. Conclusions: Disseminated cancer cells in bone marrow using quantitative RT-PCR for CEA mRNA may be a significant predictor for highly malignant squamous cell carcinoma of the esophagus. No significant financial relationships to disclose.
Identification of serum markers of glioblastoma multiforme patients using image-guided genomic and proteomic analysis
Authors: Guccione S. , Yang Y. , Chia Y. , Rubin D. , Wang Y. , Harsh G. , Atlas S. , Bednarski M. 
Published: March 2020

20008 Background: Biomarkers in serum has been demonstrated to play a critical role in caner diagnostics. Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis and low survival rate, which often has significant heterogeneity in morphology and increased vascular permeability and vessel density. In this study we identified molecules related to angiogenesis and vasculature development for GBM using a combination of contrast enhanced MR imaging, genomic and proteomic analysis, and enzyme immunoassay (ELISA). Methods: GBM patient without any prior procedures were scanned on a GE 1.5T MRI scanner using standard T1- and T2-weighted pulse sequences and gadopentetate dimeglumine as contrast agent. Samples from regions with contrast agent accumulation (contrast-enhancing, CE) and no uptake (non-enhancing, NE) were collected for microarray, Mass spectroscopic analysis and immunochemical staining. Patient serum samples were collected for protein expression quantification using ELISA assay. Results: Tissue samples from the CE and NE regions of 13 patients reveal significantly distinct gene expression patterns. Mass spectroscopy using MALDI system will also be examined. Growth factors such as laminin receptor, IGFBP-2, IGFBP-3, IGFBP-5, aFGF were all up-regulated in the CE regions, and immunohistochemical staining confirmed their protein expression. The presence of proteins with MW < 30 kD in the serum were examined using ELISA. IGFBP-2 showed to have a higher mean value (86.1 ± 29.1 ng/ml) in GBM serum as compared to healthy individuals (55.7 ± 9.9 ng/ml). Other potential markers such as IGFBP-3 and aFGF do not exhibit significant difference. Conclusions: CE-MRI using the clinical MRI agent Gd(DTPA) can reveal imaging features associated with increased vascular permeability and vessel density, and areas of fluid accumulation and necrosis. We have observed that differences in spatial resolution in the tumor correlate to changes in gene expression profiles, resulting in potential molecules that have high gene and protein expression levels in tumor area with high vascular activity and in serum. These targets can be used for diagnostic and clinical monitoring of the patient before and after therapeutic intervention. No significant financial relationships to disclose.