bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of rearranged immunoglobulin DNA in plasma
Authors: Lin L. , Gocke C. , Ambinder R. F. 
Published: March 2020

17518 Background: Tumor DNA is increasingly recognized as a marker in plasma or serum. B cells are characterized by immunoglobulin heavy chain rearrangements (IgH-R)and B cell malignancies by clonal IgH-R. We hypothesized that detection of clonal IgH-R DNA (a DNA spike) might reflect the presence of malignancy. Methods: We used a PCR and capillary electrophoresis. DNA from plasma of 6 healthy donors, 5 patients treated with rituximab, 5 persons with AIDS (PWA) but not lymphoma, 5 patients with AIDS-related lymphoma (ARL) and 5 patients with Hodgkin’s lymphoma (HL) was studied. In some cases matched peripheral blood mononuclear cells (PBMC) and followup specimens were available. Results: In plasma from healthy donors there was a normal (bell-shaped) distribution of IgH-R. In patients treated with rituximab (including a patient with an autoimmune disorder but no malignancy), IgH-R in plasma decreased by at least 100-fold. In PWA, there was a normal distribution of IgH-R. In pretreatment plasma from 2 of 5 patients with ARL, a DNA spike was detected superimposed on the background of IgH-R. The DNA spike was not detected in PBMC. In both ARL patients the spikes disappeared with therapy. However, in 1 it reappeared, and shortly thereafter the patient relapsed. Clinical relapse was associated with an increase in spike amplitude. The spike disappeared again with salvage chemotherapy. Identity of the pretreatment and relapse spikes was confirmed by sequencing. In 1 of 5 patients with HL a pretreatment DNA spike was detected in plasma. It decreased in serial specimens during the first month of combination chemotherapy. Conclusions: A normal distribution of rearranged Ig DNA is readily detected in plasma from healthy donors and patients. This normally distributed rearranged Ig DNA consistently disappears with rituximab therapy. A DNA spike can be detected in the plasma of some patients with B lineage lymphoma even when that spike is not evident in PBMC consistent with the possibility that this DNA is not derived from circulating tumor cells. The reappearance of a DNA spike may presage relapse. Further investigation will be required to determine the sensitivity and specificity of detection of such Ig DNA spikes and to confirm a tumor origin. No significant financial relationships to disclose.
Safety and efficacy of retreating follicular non-Hodgkin’s lymphoma (NHL) with 90Y ibritumomab tiuxetan
Authors: Shah J. , Harrough D. , Saville W. , Mueh J. , Lister J. , Jasthy S. , Gregory M. , McKay C. , Krumdieck R. , Forero A. 
Published: March 2020

17528 Background: There is no data regarding safety and efficacy of treating follicular NHL patients with a second course of 90Y ibritumomab tiuxetan (Zevalin). Methods: Patients with follicular NHL who received 2 courses of Zevalin therapy were identified nationally, and data was retrospectively collected. Results: 10 patients (pts) (mean age 62.5 years, 48–91) were identified. Prior to the first Zevalin, all pts received chemotherapy (mean 2.4 courses, 1–5), 3/10 auto-PBSCT, and 4/10 external beam radiotherapy(ebRT). After the initial course of treatment, the mean time to nadir for the anemia was 7.9 weeks (wks)(4–13), neutropenia was 6.7 wks (4–10); and thrombocytopenia was 5.2 wks (4–8). 1 pt required growth factor support and transfusions; 2 had an incomplete recovery of platelet count at 23 and 30 wks (76,000 and 126,000/μl). Hematologic toxicity and grades are in the table below. Prior to the second course of Zevalin 2 pts received ebRT, 1 received 131I tositumomab, and 3 received chemotherapy (1–5 regimens). The median time to the second Zevalin course was 613 days (183–1,300). After the second course of Zevalin, the mean time to nadir for the anemia was 8.2 wks (2–25); neutropenia was 6.7 wks (4–10); and thrombocytopenia was 5.5 wks (4–7). 4/10 pts required growth factor support, 2 required transfusions, 3 had incomplete recovery of platelet count and early progression, 2 pts had a maximum recovery of their platelet count at 29 and 40 wks (143,000 and 144,000/μl). There were no infectious or bleeding complications with either course of Zevalin. No secondary myelodysplastic syndrome or acute leukemia were reported. Conclusions: Retreating patients with follicular NHL with a second course of Zevalin is tolerable with substantial evidence of clinical efficacy. This data warrants further evaluation of Zevalin retreatment in a clinical trial. [Table: see text] [Table: see text]
Pharmacokinetics and efficacy of pegfilgrastim as hematopoietic support for dose-dense every-2-week chemo-immunotherapy with R-CHOP as first-line therapy in elderly patients with diffuse large B cell lymphoma
Authors: Mey U. J. , Maier A. , Kleinschmidt R. , Ziske C. , Forstbauer H. , Banat G. A. , Gorschlueter M. , Popp H. , Schmidt-Wolf I. G. , Glasmacher A. G. 
Published: March 2020

17531 Background: Recently, 6 cycles of R-CHOP-14 have been recommended as reference standard for elderly patients with diffuse large B cell lymphoma (Pfreundschuh, 2004). Pegfilgrastim as a pegylated form of G-CSF has been shown to provide rapid neutrophil recovery and facilitate dose dense chemotherapy schedules with a single administration per chemotherapy cycle. The aim of this study was to analyze pharmacokinetics of a single fixed dose of 6 mg of pegfilgrastim per cycle in a homogenous group of elderly patients with diffuse large B cell lymphoma treated with R-CHOP as first-line therapy in two-weekly intervals. Methods: Ten patients with diffuse large B cell lymphoma between the age of 60 and 80 years received a single subcutaneous injection of 6 mg pegfilgrastim 24 h after the administration of R-CHOP chemo-immunotherapy, repeated for 6 to 8 cycles in two-weekly intervals. Pegfilgrastim plasma levels as well as absolute neutrophil counts were measured every other day during the first treatment cycle and twice weekly during all consecutive cycles. Incidence and duration of grade 3/ 4 neutropenia, depth of neutrophil nadir and incidence of febrile neutropenia were assessed. Results: Median age was 73.4 years. A single 6 mg injection of pegfilgrastim 24 h after the administration of CHOP was effective to allow neutrophil recovery in 69 of 70 (98.6%) two-weekly treatment cycles. Median absolute neutrophil nadir was 0.38 G/l on day 9. Grade 3/ 4 granulocytopenia occurred in all ten patients. Mean duration of grade 3/4 neutropenia (< 1.0 G/l) was two days. Febrile neutropenia occurred in one patient. Plasma levels of pegfilgrastim remained elevated during the neutropenic phase. At the start of hematologic recovery, plasma concentrations of pegfilgrastim decreased rapidly as a result of clearance by the neutrophils. Median pegfilgrastim trough plasma level was 0.43 ng/ml on the day preceding the next application. Conclusions: A single fixed dose of 6 mg of pegfilgrastim given once per cycle of R-CHOP-14 is effective in supporting neutrophil recovery to safely allow two-weekly drug administration in previously untreated elderly patients with diffuse large B cell lymphoma. [Table: see text]
Primary cutaneous lymphomas in Peru
Authors: Beltran B. , Carrasco A. , Vera L. , Salinas E. , Ticona M. , Portugal K. 
Published: March 2020

17566 Background: The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the relative frequency of cutaneous lymphomas and to examine the clinical relevance of the new WHO/EORTC classification in Peruvian cases of cutaneous lymphoma. Methods: We conducted a clinicopathologic retrospective study of a collection of 68 primary cutaneous lymphomas, diagnosed from 1997 to 2004 in a National General Hospital. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from 67 patients with malignant lymphomas of the skin were reviewed. HTLV-1 serology was made using ELISA and Western Blot methods. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Mean age at presentation was 62 years and the female/male ratio 1.5:1. T cell lymphomas were 88.6% and 11.4% were B-cell lymphomas. The most frequent cutaneous lymphoma was mycosis fungoides (MF) 30/67 (44.7%), Adult T-cell leukemia/lymphoma (ATLL) 13/67 (19.4%), unspecified peripheral T-cell lymphoma 4/67 (6%), lymphomatoid papulosis 2/67 (3%), leg-type diffuse large B-cell lymphoma 2/67 (3%), diffuse large B-cell lymphoma 2/67 (3%), subcutaneous panniculitis-like T-cell lymphoma 2/67 (3%), anaplastic large cell lymphoma 1/67 (1.4%), Sézary síndrome 1/67 (1.4%), nasal type extranodal NK/T-cell lymphoma 1/67 (1.4%), marginal zone B-cell lymphoma 1/67 (1.4%), follicle center lymphoma 1/67 (1.4%), intravascular lymphoma 1/67 (1.4%) and unclassifiable 5/67 ( 7.4%). Clinical stages of MF were: 60% stage I; 30% stage II; 3% stage III and 7% stage IV. 5-year survival was 77%. In ATLL group, 3 had smouldering type and 10 had cutaneous type. 5-year survival was 18%. Conclusions: In this retrospective analysis, cutaneous T cell lymphomas were prevalent; both MF and ATLL had the most frequency among primary cutaneous lymphomas in our hospital. ATLL had a poor 5-year survival. No significant financial relationships to disclose.
Clinical findings in a large cohort of adult patients (pts) with Hodgkin’s disease (Hd) in Argentina: A report from two institutions
Authors: Morgenfeld E. L. , Dragosky M. , Alcaraz S. , Annetta I. , Calmet R. , Luchetta P. , Marquez M. , Gil Deza E. , Rivarola E. , Gercovich F. G. 
Published: March 2020

17570 Background: More than 20,000 new cases of HD are diagnosed each year all over Europe, Canada and the United States. Nevertheless, there are few reports in current literature showing data from large series in developing countries. Methods: The medical records of adult pts with an oncohaematologic diagnosis in two large oncological centers (HMC and IOHM) were reviewed. A period spanning the past 10 years was considered with the objective of measuring the incidence of HD. Oncologists in charge were asked to fill a form with the relevant clinical data. Results: Three hundred and fifty eight out of 1,884 medical records of pts with HD (19%) were retrieved (M: 55.2%/F: 44.8%). Seven pts were HIV positive. Bulky disease was present in 7,4%. The following table shows the main topics (See table ): Conclusions: Incidence of HD in our serie was similar to the published report. However, two important differences arose: it was not possible to notice neither the double curve described nor the usual histological subtype distribution (more MC than the expected frequency). According to previous reports, prevalence of NS was associated with mediastinal locations and younger pts. Actuarial survival must be presented. [Table: see text] No significant financial relationships to disclose.
Efficacy and safety of epoetin beta 30,000 IU once weekly in patients with solid tumors and chemotherapy-induced anemia
Authors: Heras P. , Hatzopoulos A. , Karagiannis S. 
Published: March 2020

18620 Background: Anemia is common in patients receiving chemotherapy, causing a multitude of symptoms which have a major impact on quality of life (QoL). Epoetin beta rapidly increases hemoglobin (Hb) levels and improves QoL in anemic patients with a variety of tumors. In patients with lymphoid malignancies, once-weekly epoetin beta 30,000 IU has comparable efficacy to the three-times weekly 10,000 IU regimen (Cazzola et al. Br J Haematol 2003; 122: 386–393). Methods: This was a randomized, double-blind, dose-finding study assessing the efficacy and safety of once-weekly epoetin beta in patients with solid tumors receiving chemotherapy. Adult patients with anemia (Hb levels <11 g/dl) were randomized to receive epoetin beta 30,000 IU or 20,000 IU once weekly for 12 weeks. All patients received oral iron supplementation. Hb levels, transfusion need and QoL (Functional Assessment of Cancer Therapy-fatigue subscale score [FACT-fatigue]) were assessed at regular intervals. Results: Fifty patients were randomized; 30 patients received epoetin beta 30,000 IU once weekly and 20 received 20,000 IU once weekly. Mean (± SD) increase in Hb from baseline to week 12 was 1.75 ± 2.15 g/dl in the 30,000 IU group (p = 0.008 vs baseline) and 1.04 ± 1.75 g/dl in the 20,000 IU group (p = non-significant). Hb response (increase in Hb level ≥2 g/dl from baseline) was observed in 78.3% of patients receiving epoetin beta 30,000 IU and 66.7% receiving epoetin beta 20,000 IU. Improvements in FACT-fatigue were significantly (p < 0.001) correlated with increases in Hb level. Transfusion use was low during the study in both groups. Both epoetin beta regimens were well tolerated and there were no dose-dependent adverse events. Conclusion: Epoetin beta 30,000 IU once weekly is an effective and well-tolerated treatment of anemia in patients with solid tumors. No significant financial relationships to disclose.
Imatinib mesylate therapy in advanced gastrointestinal stromal tumors—A Regional cancer centre experience
Authors: Patel K. M. , Shah P. M. , Shukla S. N. , Parikh B. J. , Anand A. S. , Shah S. A. , Talati S. S. , Panchal H. P. , Pandey R. 
Published: March 2020

19505 Background: The treatment of gastrointestinal stromal tumors has been revolutionised by the advent of Imatinib, a specific tyrosine kinase inhibitor. Post operative local and metastatic recurrences of this tumor have been effectively managed by Imatinib. Here we present our experience of Imatinib in recurrent locally advanced/metastatic gastrointestinal stromal tumors (GIST). Methods: From Nov 2001 to Sep 2005, 33 patients with metastatic and / or locally advanced inoperable CD-117 positive GIST were offered imatinib mesylate therapy at 400 mg/day p.o. A total of 21 patients were evaluable for tumor response. Follow up period ranged from 4 months to 38 months with median follow up period being 18 months. Median age is 58 yrs, M:F ratio is 6:4. ECOG performance status was 0–1 in 70% (23 patients) and 2 in 30% (10 patients). 70% patients had post surgery recurrence. 2 patients (6%) had received adjuvant chemotherapy prior to recurrence. 30% (10 patients) had local recurrence, 40% (13 patients) had metastatic disease while 30% (10 patients) had local recurrence as well as metastatic disease. Results: Response evaluation was done by RECIST criteria. 15% (5 patient) showed CR while PR rates were 30% (10 patients). The overall major response (CR+PR) was 45%. The overall progression free survival was as high as 80%. All the patients who had a progression free survival also had a significant improvement in quality of life. Conclusions: Imatinib mesylate therapy shows significant survival benefits in locally advanced inoperable/metatstatic gastrointestinal stromal tumors. It will be a very long time before PET scan for evaluation and follow up becomes feasible in developing country setting. No significant financial relationships to disclose.
Frequency of histopathologic types of soft tissue sarcoma (STS) reported from a large community-based hospital over a 20 year period
Authors: Nair S. G. , Amadio C. H. , Scarlato M. , Forman D. A. 
Published: March 2020

19507 Background: Soft Tissue Sarcomas (STS) are rare tumors primarily of mesenchymal origin. The World Health Organization recognizes more than 50 subtypes of STS. Previously reported frequencies of histopathologic types of STS come from a handful of large cancer centers. The incidence of tumor types seen at large cancer treatment centers do not necessarily reflect the histologies seen at community hospitals. We sought to determine the frequency of histopathologic types of adult STS seen at our large community-based hospital. Methods: We performed a search of our tumor registry from the year 1984 through 2004 looking for histologic types of non-GIST STS involving the peripheral nervous system, autonomic nervous system, retroperitoneum, peritoneum, other connective and soft tissue locations. Our tumor registry is certified through the American College of Surgeons. Our pathologist are board certified, highly skilled, and commonly refer pathologic specimens for second opinion if a histologic diagnosis is in doubt. The 10 most common histologies diagnosed are reported. Results: Our hospital diagnosed and treated 250 STS over this 20 year period. The histologic type of sarcoma by number and percent of total cases is as follows: Malignant fibrous histiocytoma 60 (24%), Liposarcoma 51 (20%), Leiomyosarcoma 38(15%), Sarcoma N.O.S. 18(7%), Hemangiosarcoma 15 (6%), Synovial Sarcoma 10 (4%), Rhabdomyosarcoma 9 (4%), Fibrosarcoma 9 (4%), Spindle Cell Sarcoma 7 (3%), and Giant Cell Sarcoma 3 (3%). Conclusions: The frequency of the most common histologic types of soft tissue sarcoma seen at our community hospital is quite consistent with that previously reported in the literature from large referral-based cancer centers. There does not appear to be an influence of selection bias in previous reports of relative frequency of histopathologic types of STS. No significant financial relationships to disclose.
Changes in serum P1NP, BAP, CTX-1, and YKL-40 following hormonal treatment for metastatic prostate carcinima are related to survival
Authors: Brasso K. , Iversen P. , Johansen J. , Teisner B. , Garnro P. , Pri Ce P. , Christensen I. J. 
Published: March 2020

20002 Background: Previously it has been demonstrated that elevated P1NP, BAP, CTX-1, and YKL-40 levels at the time of diagnosis in patients with metastatic prostatic carcinoma were associated with survival. This study presents a follow-up to evaluated the prognostic value of thes biomarkers in a time-dependent analysis. Methods: Serum P1NP, BAP, CTX-1, and YKL-40 were determined in 106 patients with newly diagnozed metastatic prostatic carcinoma following start of either total androgen ablation or parenteral estrogen theraphy. Results: After 6 months of treatment significant decreases in P1NP, BAP, and YKL-40 were found. Univariate Cox analysis demonstrated that 6 month levels of P1NP, BAP, and CTX-1 were significantly associated with survival. In a multivatiate analysis using tumormarker levels at 6 months after start of treatment demonstrated that Soloway score (HR=3.9), WHO grade (HR=3.9), and P1NP (HR=2.2) all were significant predictors of survival. When using the biomarkers mentioned above as time-dependent co-variates in univariate COX regression analysis it could be shown that increasing levels og P1NP, BAP, and YKL-40 alle were significant predictors of early death. Conclusions: Serial monitoring of serum P1NP, BAP, CTX-1, and YKL-40 in patients with metastatic prostatic carcinoma during hormonal treatment provide information on prognosis. No significant financial relationships to disclose.
Risk assessment in high grade sarcoma patients during neoadjuvant chemotherapy using multiple tracer PET
Authors: Eary J. F. , Conrad E. , Link J. , Cizik A. , Mankoff D. , Krohn K. 
Published: March 2020

20006 Background: Patients with high grade soft tissue sarcomas are treated with neoadjuvant chemotherapy. Sarcomas have biological features that may predict for poor outcome. Some of these features are tumor proliferation rate, level of tumor hypoxia, and upregulation of tumor drug resistance mechanisms. Methods: We have a group of specific PET imaging agents to quantify the level of activity of these tumor processes. Patients with soft tissue sarcomas receive [C-11]Thymidine (TdR) to assess cellular proliferation, [O-15] Water to quantify tumor blood flow and to serve as the input function for quantification of the other tracers, [C-11]Verapamil to assess drug resistance mechanism activity, and [F-18]Fluoromisonidazole) FMISO to quantify changes in tumor hypoxic volume in response to treatment. These studies are performed in a single PET imaging session prior to neoadjuvant chemotherapy, after the second of four cycles of therapy and in the week prior to resection. Results: An example of this complex study result, is demonstrated by a recent patient with a high grade soft tissue sarcoma. The tumor showed increased TdR uptake, a moderate hypoxic volume, and [C-11] verapamil uptake prior to initiation of neoadjuvant adriamycin based chemotherapy. After 2 cycles of therapy, there was a significant decrease in the maximum level and volume of TdR uptake and a large reduction in tumor hypoxic volume. Conclusions: These data would imply a high risk soft tissue sarcoma due the presence of increased cellular proliferation, a significant hypoxic volume and the absence of p-glycoprotein activity determined by the presence of [C-11]Verapamil uptake. However, early response is also suggested by the findings above. Patient outcome will be assessed and correlated with these tumor parameters to further understand what tumor biological risk factors can be quantified non-invasively and repeated throughout the clinical course in soft tissue sarcoma patients. Supported by NIH NCI PO1 42045–18 and S10 RR017229–01 [Table: see text] No significant financial relationships to disclose.
Phase I clinical and pharmacokinetic (PK) trial of the kinesin spindle protein (KSP) inhibitor MK-0731 in cancer patients
Authors: Stein M. N. , Rubin E. H. , Scott P. D. , Fernandez R. , Agrawal N. G. , Hsu K. , Walker A. , Holen K. , Wilding G. 
Published: March 2020

2001 Background: KSP is essential for the separation of spindle poles during mitosis and inhibition results in mitotic arrest. Function is thought to be limited to mitosis and inhibitors should not cause the peripheral neuropathy seen with other mitotic-inhibitors. MK-0731 is a potent inhibitor of KSP, with an IC50 of 2.2 nM, and >20,000 fold selectivity against other kinesins. MK-0731 causes mitotic arrest with an EC50 in several tumor cell lines of 3−5 nM. Methods: Phase I study to determine the safety and tolerability, MTD, and PK of MK-0731 administered IV over 24 hrs every 21 (Q21) ds. Results: Eight pts with solid tumors (M/F 6/2), median age 55 yrs (45–72 yrs), were treated at doses of 6 to 48 mg/m2/24hrs. Prolonged (≥5 ds) Grade 4 neutropenia was observed in 2 pts at 48 mg/m2/24 hrs leading to expansion of cohorts at lower dose levels. Other drug related toxicities include diarrhea, alopecia, nail changes, nausea/vomiting, mucositis, abdominal pain, anorexia, phlebitis. PK results suggest that steady-state concentrations may not be achieved by the end of the 24 hr infusion and MK-0731 concentrations appear to decline monoexponentially or biexponentially following the infusion with terminal t1/2 from ∼4 to 11 hrs. Median values at the 48 mg/m2/24 hrs dose level were Cmax = 1223 nM, AUC∞ = 26.585 μM · hr, and CL=122 mL/min. AUC, exposures, and end of infusion concentrations appear to increase proportionally with dose. Conclusions: This is the first study of MK-0731. The MTD was exceeded at 48 mg/m2/24 hrs Q21. Further evaluation will continue at lower doses. [Table: see text]