bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of serum interleukin-2 receptor value for diagnosis of malignant lymphoma.
Authors: Nakata Masanobu , Ara Takahide , Shima Kanako , Minauchi Koichiro , Ota Shuichi , Imai Kiyotoshi , Hirano Teiichi , Kiyama Yoshio , Kobayashi Naoki , Imamura Masahiro 
Published: March 2020

e19507 Background: Serum soluble interleukin-2 receptor (sIL2R) has been anecdotally used for diagnosis of malignant lymphoma (ML). However, sensitivity and specificity have not been evaluated; therefore, there is no consensus for the appropriate cut-off value for diagnosis of ML. Methods: We retrospectively analyzed sIL2R values at initial presentation in the patients who were diagnosed with ML. We compared them with the sIL2R values in the patients who presented with lymphadenopathy but were not diagnosed with ML. Results: In 496 patients with ML, 232 patients were diagnosed with diffuse large B-cell lymphoma (DLBCL), 109 with follicular lymphoma (FL), 40 with T-cell lymphoma (TCL), 39 with Hodgkin lymphoma (HL), 16 with marginal zone B-cell lymphoma (MZBCL), 12 with mantle cell lymphoma (MCL) and 21 with others. In the 69 control patients who did not have ML, 22 patients were diagnosed with metastatic lymph nodes of cancer, 14 with reactive lymph nodes, 12 with Kikuchi’s disease (histiocytic necrotizing lymphadenitis), 6 with granulomatous lymphadenitis (including mycobacterial infection), 3 with sarcoidosis, 2 with infectious mononucleosis (in combination with clinical diagnosis), 1 with Castleman’s disease and 9 with others. Mean value of sIL2R in the patients with ML was 4223U/ml (95% confidence interval, CI: 3251-5196). It was significantly higher than that in patients not having ML (mean: 1072U/ml, 95%CI: 788-1356, p<0.0001, t-test). The sensitivity and specificity were calculated based on our results. When the cut-off value was set at 1000U/ml, sensitivity for diagnosis of ML was 64% and specificity was 68%. When the cut-off value was set at 2000U/ml, sensitivity was 41% and specificity was 86%. According to histologic subtypes, mean sIL2R values were 4592U/ml (95%CI: 3690-6088) in DLBCL, 2166U/ml (95%CI: 1669-2664) in FL, 6510U/ml (95%CI: 3692-9329) in TCL, 1395U/ml (95%CI: 550-2240) in MZBCL, 2956U/ml (95%CI: 1736-4175) in HL and 3264U/ml (95%CI: 1734-4795) in MCL. Mean sIL2R value in each histologic subtype, except for MZBCL, was significantly higher than that in patients not having ML. Conclusions: Our study suggests that sIL2R value is useful for diagnosis of ML other than MZBCL.
Prolonged therapy with single-agent bortezomib (btz) in four patients (pts) with relapsed primary systemic AL amyloidosis treated in the CAN2007 phase II study.
Authors: Kukreti Vishal , Pei Lixia , Enny Christopher , Esseltine Dixie , Van De Velde Helgi , Cakana Andrew , Reece Donna E 
Published: March 2020

e19509 Background: CAN2007 was the first prospective study of single-agent btz in relapsed AL. We describe 4 pts in CAN2007 (NCT00298766) who received btz treatment for up to 5.6 yrs. Methods: 70 pts received btz 0.7–1.6 mg/m2, d 1, 8, 15, 22, 35-d cycles (QW), or 0.7–1.3 mg/m2, d 1, 4, 8, 11, 21-d cycles (BIW), for up to 8 cycles; prolonged treatment was permitted at the discretion of the treating physician for pts showing ongoing clinical benefit. Results: Pt #1 (male, age 53 yrs; IgA lambda AL with cardiac and renal involvement; 16 mos since diagnosis; prior therapy: melphalan plus ASCT) received btz 1.3 mg/m2 QW for 57 cycles (5.6 yrs). Cumulative dose was 190.5 mg/m2. He had a hematologic CR to initial btz therapy and a complete renal response to sustained therapy, without grade 3/4 adverse events (AEs). Pt #2 (male, age 53 yrs; IgG kappa AL with gastrointestinal [GI] involvement; 38 mos since diagnosis; prior therapy: ASCT) received btz 0.7 mg/m2 BIW for 47 cycles (4.3 yrs; cumulative dose 77.7 mg/m2), had a hematologic response of stable disease, and had a renal response, with no grade 3/4 AEs. The pt progressed and is in remission on alternative therapy. Pt #3 (female, age 55 yrs; IgG lambda AL with GI and other-site involvement; 14 mos since diagnosis; prior therapy: ASCT) received btz 1.6 mg/m2 QW for 39 cycles (3.7 yrs; cumulative dose 167.7 mg/m2). She had grade 3 paralytic ileus in cycle 8 with dose adjustment to 1.3 then 1.0 mg/m2. She had a hematologic PR. Pt #4 (female, age 54 yrs; lambda light-chain AL with cardiac and GI involvement; 44 mos since diagnosis; prior therapy: cardiac allograft followed by ASCT) received 57 cycles (3.5 yrs; cumulative dose 173.7 mg/m2); starting dose was 1.3 mg/m2 BIW, reduced to 1.0 (cycle 3) and 0.7 mg/m2 (cycle 16) due to grade 3 AEs of vasculitis and volvulus, respectively. Other grade 3 AEs included pneumonia, hemoptysis, and C. difficile diarrhea. Best hematologic response was PR; a renal response was also achieved. Conclusions: This case series indicates the feasibility and activity of btz for long-term disease control in relapsed AL, particularly in pts who did not achieve a CR to initial btz therapy. Pts 1, 3, 4 remain progression-free and are ongoing on btz. Clinical trial information: NCT00298766.
Barriers to enrollment of patients with recurrent diffuse large B-cell lymphoma (DLBCL) in clinical trials.
Authors: Marton Ashley , Assouline Sarit E. , Kezouh Abbas 
Published: March 2020

e19520 Background: Research into novel therapies for relapsed/refractory DLBCL may be hindered by the perception these patients are difficult to capture in clinical trials. We performed a retrospective analysis of all DLBCL at our institution from 01/2006 to 03/2012 to identify hurdles to trial enrolment. Methods: All DLBCL cases were identified through the hospital tumor registry. Patients were included in the analysis if they had any diagnosis of DLBCL relapsed or refractory to standard therapy. Baseline demographic and clinical characteristics, details of treatment, responses, relapse, evaluation for clinical trials and participation in clinical trials were determined by review of hospital charts. Results: Of a total of 284 patients, 76 had relapsed/refractory disease, 10 of 20 had a successful ASCT, and there is insufficient data on 1 patient. Of the remaining 65, 11 (17%) made it to trial. The median age was 65, 34 were male, median number of prior therapies was 2, 74% had at least one comorbidity and 46% had at least 2, 62% of patients had de novo DLBCL, 18% transformed and 20% composite. 81% of cases were discussed at tumor board. Reasons for failing to enroll on trial included prohibitive comorbidity (21%), rapid progression (15%), decision for palliation (15%), prior second malignancy (9%), thrombocytopenia (13%), CNS disease (9%), proximity to ASCT (2%), no protocol for DLBCL (6%), palliative radiation (6%). Conclusions: We demonstrate that 17% of patients with DLBCL not responding to standard therapy make it to trial, the remainder does not mainly beacause of comorbidity and rapid progression. Similar barriers were found for solid tumor patients (Lara, JCO 2001) and a similar accrual rate was seen in relapsed non-small cell lung cancer (Baggstrom,J Thor Oncol 2011) . Relapsed DLBCL is a population for whom clinical trial research is challenging but possible.
Follicular lymphoma in the elderly: A different disease?
Authors: Rubio Judit , Franco Fernando , Ruiz-Valdepeñas Andrea , Palka Magda , Almagro Elena , Perez David , Mendez Miriam , Cantos Blanca , Millán Isabel , Provencio Pulla Mariano 
Published: March 2020

e19532 Background: The aim of this study was to evaluate the characteristics of patients older and younger than 70 years diagnosed with follicular lymphoma (FL). Methods: A review of the clinical database of 131 patients with LF treated in our hospital between May 1980 and January 2013 was performed. Clinical, treatment, and following items were obtained. Results: 34 patients were 70 years of age or older (70.6 to 83.9 years) and 98 were younger (23-69.3 years), without significant differences with respect to gender, histology grade, stage and Performance Status. The extranodal involvement sites in the younger group were more frequent in spleen (17.1%), liver (17.1%), bowel (14.3%) and head and neck (11.4%), meanwhile in the eldest were in lung (35.7%), bone (21.4%) and pleura (14.3%), with significant differences (p=0.007). The median Overall Survival (OS) was 8.1 years (1.2-31.4) in the younger group and 4.3 years (1.2-7.2) in the older group. The median of probability of Free Progression Survival (FPS) was 3.2 years (0.1-31.4) in younger patients and 1.7 years (0.1-5.5) in older patients. It exists significant differences in the probability of OS and FPS (both p<0.001), with worse results in older patients. The analysis of the causes of death (FL, second tumour or other causes) does not demonstrate significant differences between both groups. Differences were not found between the age groups when CHOP versus CVP was used. Not using rituximab in addition to CHOP scheme implies a relative risk of relapse of 3.3 (95% IC 1.5-6.9 p<0.001). Conclusions: It should be noted a worse OS and FPS in the older population. Nevertheless, the different extranodal involvement suggests a different biologic behaviour in both groups. [Table: see text]
Rituximab, gemcitabine, cisplatin, and methylprednisolone (R-GEM-P) in treatment of relapsed diffuse large B-cell lymphoma (DLBCL).
Authors: Barton Sarah Rachel , Hawkes Eliza Anne , Cunningham David , Peckitt Clare , Chua Sue , Wotherspoon Andrew , Attygalle Ayoma , Horwich Alan , Dearden Claire E. , Potter Mike , Chau Ian 
Published: March 2020

e19543 Background: Patients with DLBCL who relapse after 1st line therapy have poor prognosis. Although there is limited evidence for benefit of rechallenging patients with rituximab, this is considered justified by minimal toxicity and potential outcome improvement. GEM-P+/-R is an accepted salvage regimen, with merits of outpatient delivery and mainly non-overlapping toxicity with 1stline therapy, but there are relatively few reports of its efficacy and tolerability. Methods: We performed a retrospective single centre analysis of all patients meeting the following criteria: age≥18, histologically proven DLBCL, ≥1 FDG-PET, treated between 2001-2011 with GEM-P+/-R (gemcitabine 1000mg/m2 D1, D8, D15, methylprednisolone 1000mg D1-5, cisplatin 100mg/m2 D15 every 28 days +/- rituximab 375mg/m2 D1 & D15) or GEM-CARBO+/-R (cisplatin substituted for carboplatin AUC5). Data were collected on patient and treatment characteristics, response evaluated by modified IWG 2007 criteria (FDG-PET +/- CT), survival, and toxicity (CTCAE v4.0). Results: We identified 74 patients with median age 56 (range 25-79) who received a median of 3 cycles (range 1-6) of either GEM-P (89%) or GEM-CARBO(11%), combined with rituximab in 69%. 41% had transformed indolent lymphoma. Overall response rate (ORR) was 49% (complete response (CR) 16%, partial response (PR) 32%). Among 40/74 patients evaluated with FDG-PET, metabolic ORR was 63% (mCR 23%, mPR 40%). Of 51/74 patients treated in 2ndline, ORR was 45%. Significantly higher ORR was observed in patients treated with R-chemotherapy (61% vs 22%, p=0.002), despite 88% having received prior rituximab. 17 patients proceeded to autologous transplant. With median follow up of 50.5 months, 3 yr overall survival in all patients from start of GEM-P was 39% and 3 yr progression free survival 19%. Predominant Grade≥3 toxicity was haematological; thrombocytopenia 69%, neutropenia 58%, anaemia 15% and febrile neutropenia 8%. Conclusions: R-GEM-P is an effective salvage regimen in DLBCL, with the convenience of outpatient delivery. Despite previous rituximab exposure, patients in our cohort benefited from the addition of rituximab, supporting current practice.
Hypofractionated adjuvant radiation therapy of soft tissue sarcoma in elderly patients.
Authors: Merimsky Ofer , Soyfer Viacheslav , Corn Benjamin W. , Dadia Solomon , Kollender Yehuda 
Published: March 2020

e21521 Background: Adjuvant radiation therapy is an essential part of combined limb sparing treatment of STS. The recommended dose of radiation lies in the range of 60 Gy in standard fractionation of 1.8-2 Gy. Elderly or medically unfit patients often have difficulty in completing 6-7w of daily treatment. A prolonged course of radiation may be interrupted by acute side effects, which sometimes demands further extension of the overall course or even discontinuation of treatment. We intended to evaluate the efficacy of a hypofractionated adjuvant approach with radiation therapy for STS in the elderly and debilitated patients. Methods: 21 elderly patients were treated with a short course of adjuvant RT (39 to 48 Gy, 3 Gy per fraction) for STS. The medical records of the patients were retrospectively reviewed for the local or distant recurrence and side effects of RT. Results: Overall, the hypofractionated irradiation regimen of 39-48 Gy in 13-16 fractions was well tolerated with only 3 patients developing Grade 2-3 acute toxicity (mainly dermatitis). Three patients suffered from delayed Grade 2-3 toxicity (chronic pain, skin atrophy, teleangiectasiae) scaled according to CTSC. The mean time from the surgery until the initiation of RT was 65 days (SD 21.6). Mean RT time was 18.4 (SD 3) days. No delay of treatment due to acute toxicity was registered. All patients except for one were able to receive RT in the ambulatory setting. With a mean follow-up of 532 days (SD: 325), three local recurrences (14%) were detected. Three of eight patients with distant metastases died of sarcoma (graph 1). One patient with metastatic disease in the lung received salvage stereo tactic radiation therapy and was still alive 6 month after completion of SBRT with no evidence of disease. At a mean 532 days of follow up three local recurrences (14%) were detected .Eight patients (38%) had lung metastases during the observed period. Three of them died from metastatic disease. The hypofractionated radiation was well tolerated with minimum long term side effects. Conclusions: Hypofractionated adjuvant radiation appears to be an effective treatment in terms of local control in elderly and debilitated patients.
Gene fusions evidence in a KIT/PDGFRA wild-type GIST without mutations in SDH units identified by a whole transcriptome study.
Authors: Urbini Milena , Astolfi Annalisa , Indio Valentina , Saponara Maristella , Nannini Margherita , Lolli Cristian , Mandrioli Anna , Gatto Lidia , Pallotti Maria Caterina , Biasco Guido , Pantaleo Maria A. 
Published: March 2020

e21523 Background: A subset of KIT/PDGFRA wild-type GIST (WT) harbour mutations in SDH units. In the majority of the remaining cases of WT GIST no other molecular events are identified.We performed a RNA-seq in a WT GIST without mutations in SDH genes using next generation approach to discover molecular events in this GIST population. Methods: In 2003, a 63-year old woman underwent surgery for an ileal GIST (size 6 cm, MI 6/50HPF).After 6 years, she developed a recurrence with a single hepatic lesion. The KIT and PDGFRA analysis of the lesion did not show mutations. Therefore, she did not receive imatinib but she underwent a surgical removal. The analysis of all SDH units did not show mutations. So paired-end RNA-seq (75X2) was performed with Illumina HiScanSQ platform. After mapping the short reads on the human genome(HG19), SNVs and InDels were called by SNVMix2 with an accurate filtering procedures including predictors of mutations effect at protein level. Gene fusions discovery was done considering the agreement between DeFuse, ChimeraScan and FusionMap tools and validated by SangerSequencing using primers spanning the mRNA breakpoints. Results: Four different gene fusions and 206 non-synonymous SNVs were discovered, of which 62 were called deleterious by at least one predictor, and they are undergoing further validation. SPRED2-NELFCD gene fusion originated from an interchromosomal translocation-inversion between chr 20 and 2. The event involved exon1 of SPRED2 and exon11 of NELFCD, probably leading to inactivation of both genes. NELFCD encodes a component of the NELF complex that negatively regulates transcription elongation by RNA pol II, while SPRED2 is a member of the Sprouty /SPRED family that repress growth factor-induced activation of the MAPK/ERK pathway. The other three events were intrachromosomal aberrations: MARK2-PPFIA1 and PLA2G16-ATL3 on chr 11 and ASCC1-C10orf11 on chr 10. Only the first event led to an in-frame fusion (MARK2 ex1- PPFIA1 ex2) probably dysregulating the expression of the downstream gene. Conclusions: This is the first evidence of gene fusions in GIST. The oncogenetic role and the tumor frequency of these events deserve to be studied.
Salmonella typhimurium A1-R targets chemoresistant stem-like human pancreatic cancer cells.
Authors: Hiroshima Yukihiko , Zhao Ming , Zhang Yong , Maawy Ali , Hassanein Mohamed K. , Suetsugu Atsushi , Chishima Takashi , Tanaka Kuniya , Bouvet Michael , Endo Itaru , Hoffman Robert M. 
Published: March 2020

e22011 Background: Salmonella typhimurium A1-R can selectively target tumors. XPA1 human pancreatic cancer cells are dimorphic (spindle and round shape); the spindle-shaped cancer cells have stem-like properties (J Cell Biochem 112, 3549-3554, 2011). Methods: Serial dilution was performed to obtain clones of both cellular morphologies. To determine chemosensitivity, in vitro IC50 values were obtained for both types of XPA1 cells for (1) Cisplatin (CDDP); (2) 5-fluorouracil (5-FU); (3) Gemcitabine (GEM); and (4) S. typhimurium A1-R. The efficacy of these drugs was also determined for both types of XPA1 cells in vivo. Results: IC50 values of spindle-shaped and round XPA1 cells, respectively, were 2.65 ± 0.22 μg/ml and 1.43 ± 0.36 μg/ml for CDDP (p = 0.012); 2.44 ± 0.25 μg/ml and 1.48 ± 0.19 μg/ml for 5-FU (p = 0.007); 3.17 ± 0.15 ng/ml and 2.70 ± 0.29 ng/ml for GEM (p = 0.133); and (19.7 ± 1.46) x 108 cfu/ml and (17.8 ± 9.78) × 108 cfu /ml for S. typhimurium A1-R (p = 0.771). In vivo, 5-FU and A1-R significantly reduced the tumor weight of round cells (5-FU; p = 0.028; S. typhimurium A1-R; p = 0.011). However, only S. typhimurium A1-R significantly reduced the tumor weight of spindle-shaped cells (p = 0.012). Conclusions: The spindle-shaped stem-like XPA1 cells were thus chemo-resistant but sensitive to S. typhimurium A1-R, suggesting S. typhimurium A1-R could be a promising therapy for chemo-resistant human pancreatic cancer stem-like cells.
Salmonella typhimurium A1-R effectively targets human-patient pancreatic tumorgrafts in nude mice.
Authors: Zhao Ming , Katz Matthew H. G. , Fleming Jason B. , Suetsugu Atsushi , Zhang Yong , Maawy Ali , Chishima Takashi , Tanaka Kuniya , Bouvet Michael , Endo Itaru , Hoffman Robert M. , Hiroshima Yukihiko 
Published: March 2020

e22012 Background: Genetically-modified Salmonella typhimurium A1-R selectively targets tumors of cancer in mouse models of human cancer. The aim of this study was to determine the efficacy S. typhimurium A1-R on human-patient pancreatic tumorgrafts growing orthothopically in nude mice. Methods: Pancreatic-cancer-patient tumor specimens were initially established subcutaneously in NOD/SCID mice immediately after surgery. The patient tumors were then harvested from NOD/SCID mice and passed orthotopically in transgenic nude mice, expressing fluorescent proteins in order for the tumors to acquire fluorescent stroma for imaging. After confirmation of tumor growth by fluorescence imaging, the nude mice were treated in the following groups: (1) 5-fluorouracil (5-FU) (10 mg/kg, ip); (2) cisplatin (CDDP) (10 mg/kg, ip); (3) gemcitabine (GEM) (150 mg/kg, ip); (4) S. typhimurium A1-R (1.5x108 cfu/body, ip); and (5) PBS (vehicle/control) (ip). Control, 5-FU, CDDP, GEM and S. typhimurium A1-R injections were performed on a weekly basis from day-21 after tumor implantation for 4 weeks. Animals were sacrificed at 7 weeks, and tumors were harvested for analysis. Each treatment arm involved 5 tumor-bearing mice. Results: No significant effects on body weight, morbidity, or severe toxicities were observed in any treatment arm. The tumor weight of each group was as follows: (1) 5-FU, 0.044 ± 0.027g; (2) CDDP, 0.04 ± 0.032g; (3) GEM, 0.058 ± 0.051g; (4) S. typhimurium A1-R, 0.106 ± 0.038g; and (5) PBS control, 0.258 ± 0.209g. S. typhimurium A1-R treatment significantly reduced the tumor weight compared to control treatment (p = 0.011), as did the other treatments including 5-FU (p = 0.005), CDDP (p = 0.004), and GEM (p = 0.001). Conclusions: S. typhimurium A1-R treatment was effective on human pancreatic tumorgrafts and should be tested in combination with chemotherapy.
Effect of p53 gene transfection on human hepatocarcinoma cells' sensitivity to irradiation.
Authors: Tao Zhengchao , Qian Liting 
Published: March 2020

e22018 Background: Several studies demonstrated that p53 gene transfection enhanced the anti-tumor effects of radiotherapy. This study is to investigate whether p53 gene transfection can increase the radiosensitivity of liver tumor cells. Methods: Liver tumor cell lines, HepG2 (with wild type p53 genes) and PLC/PRF/5 (with mutant p53 genes), were separately transfected with recombinant adenoviral human p53 gene (rAdp53) and adenoviral enhance green fluorescent protein gene (AdEGFP), forming 4 types of cells: HepG2 transfected with rAdp53, HepG2 with AdEGFP, PLC/PRF/5 with rAdp53, and PLC/PRF/5 with AdEGFP. The transfected and untransfected HepG2 and PLC/PRF/5 cells were irradiated with 6MV-X at doses of 0, A2, A4, A6, A8, A and 10 Gy. After exposition to radiation, cell survival, clonogenic capacity, and apoptosis were analyzed. The effect differences between cell types were analyzed using statistical methods of pairwise group comparisons and mixed effect model. Results: After exposing irradiation, all the cells’ survival rate and clonogenic capacity decreased, and the proportion of apoptotic cell increased. These effects become stronger with increaseing dose of radiation. Between untransfected cells, radiation had a stronger effect on HepG2 cells than PLC/PRF/5 and the differences were statistically significant for all the 3 measures. The rAdp53 transfection, not the AdEGFP, significantly enhanced radiation effects on both cell lines. The enhanced effects on PLC/PRF/5 cells were significantly stronger then the enhanced effects on HepG2 cells. Conclusions: PLC/PRF/5 cells with mutant p53 genes were more resistant to radiation then HepG2 with wide type of p53 genes. The rAd-P53 transfection could enhance radiosensitivity of both cell lines, but the enhanced effect on PLC/PRF/5 cells with mutant p53 gene was stronger than HepG2 with wide type of p53 genes.