bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is rituximab-based chemotherapy a standard practice in the treatment of B-NHLs in the developing world.
Authors: Kota Rajesh , Linga Vijay Gandhi , Gullipalli Muralidhar , Kalpathi Krishnamani , Goteke Vamshi Krishna Reddy , Maddi Rahul Narayan , Ganta Ranga Raman , Arigela Ravi Sankar , Nasaka Srividya , Gundeti Sadashivudu , Digumarti Raghunadharao 
Published: March 2020

e19533 Background: B Non Hodgkin Lymphoma (B-NHL) constitutes 90% of all NHLs. Surface CD20 is expressed in most of them. Standard of care worldwide for B NHLs currently is rituximab-based chemotherapy. In the present era, still rituximab-based chemotherapy is seldom used in India. We tried to analyze the proportion of eligible patients who received rituximab during their first line treatment and their outcome. Methods: We retrospectively analyzed all the cases of NHL patients registered at our center from 2001 to 2010. We defined “Refusal to treatment” as rejection of any therapeutic intervention, “abandonment” if treatment was initiated but not completed, “lost to follow up” as patients who have completed treatment, but missed the subsequent appointments. Results: A total of 1,351 cases of NHLs were registered during 2001-2010. B-NHLs constituted 90.6%. DLBCL accounted for 78.2% of all B-NHLs followed by follicular lymphoma (14.6%). Out of the 1,216 B-NHL patients registered, less than a third (377/1216 i.e 31%) were started on treatment, rest (69%) refused treatment. Four-fifths (79.3%) of the patients could complete at least 4 cycles of the intended chemotherapy, whereas 20.7% of them abandoned treatment in between. Rituximab-based chemotherapy could be initiated in only a quarter (94/377, 24.9%) of the eligible patients, out of which 68% (65/94) completed at least 4 cycles. Chemotherapy without rituximab was initiated in the remaining 75.1% of the patients, of which 78%(221/283) could complete at least 4 cycles. Among the 65 patients who completed at least 4 cycles of rituximab-based chemotherapy, 52% (34/65) were still alive without any evidence of disease as compared to 19% (42/221) of the patients who received chemotherapy without Rituximab at a median follow up of 17 months (range 1-125 months) p<0.05. The proportion of patients who were lost to follow up with evidence of disease at their last visit in the clinic was 4%(3/65) vs. 39%(86/221), in the rituximab vs. non-rituximab-containing chemotherapy groups respectively. Conclusions: Only 7.7% (94/1216) of the eligible B-NHL patients were able to receive rituximab-based chemotherapy. A distinct survival advantage is noted in patients who received rituximab.
Multiplexed IHC analysis to enable Hodgkin lymphoma differential diagnosis on a single slide.
Authors: Weiss Lawrence , Bordwell Alexander , Corwin Alex , Henderson Dave , Hollman- Hewgley Denise , Kenny Kevin , Lazare Michael , McCulloch Colin , Seppo Antti 
Published: March 2020

e19536 Background: Routine diagnosis of classical Hodgkin lymphoma is performed with a panel of immunohistochemistry markers to evaluate the biomarker expression profile of the relatively rare Hodgkin cells. One of the key challenges of this technique is that serial immunostains are used and hence it can be difficult or impossible to locate the same Hodgkin cell on adjacent slides. Given the rarity of the Hodgkin cells coupled with the number of markers that are needed for a definitive diagnosis, we developed a new technique in which a single patient slide is multiplexed with nine different antibodies . Methods: One FFPE tissue section from 11 cases was probed for the following nine biomarkers: CD30, CD15, CD45, Pax5, CD20, CD79a, OCT2, Bob1, and CD3. An initial 10x whole slide fluorescent image of CD30 was acquired and presented to the pathologist who based on this staining selected regions of interest for higher magnification (40x) imaging of the CD30 and the other antibodies. The fluorescent images acquired were processed for interpretation using an in-house developed viewing tool. The pathologist was able to view each biomarker as a standard grayscale, monochromatic image, an overlay of two or more biomarkers, or as a virtually created molecular DAB image. Results: A correct diagnosis of classical Hodgkin lymphoma vs. other was able to be made using the MultiOmyx platform in all cases. Subjectively, the pathologist noted that the novel methodology allowed for a significantly more confident assessment of marker expression on the Hodgkin cells in the seven cases of classical Hodgkin lymphoma, eliminating many issues of staining ambiguity and allowing recognition of subtle nuances of staining intensity in the Hodgkin cells. The CD30+ cells in the four other cases, three cases of B-cell lymphoma and one case of lymphocyte predominance Hodgkin lymphoma, showed a B-cell profile that was distinguishable from the classical Hodgkin cell phenotype. Conclusions: This new method of fluorescent multiplexing on a single tissue section allows more accurate interpretation of the biomarker expression profile on the same Hodgkin cell. It is likely that this paradigm can be expanded to a greater range of challenging cases in hematopathology.
Prognostic factors for overall survival in non-Hodgkin lymphomas: Nonlinear effect of continuous covariates.
Authors: Flores Claudio J. , Casanova Luis Augusto 
Published: March 2020

e19538 Background: To evaluate prognostic factors in patients with primary non-Hodgkin lymphomas (NHL). Methods: We retrospectively analyzed prognostic factors (PFs) for overall survival (OS) in 2160 patients (pts) with NHL treated at INEN between 1990-2002. PFs were determinate according to Cox model with P-splines. Results: The median age was 54 years (range 14 - 96) and 51% were male. The majority of the pts had good performance status (73%, WHO 0-1). The Ann Arbor stage was I-II in 51%, III-IV in 49% and B symptoms were present in 38% of the pts. The hemoglobin (Hb) was low in 48%. Leukocytes (WBC), lymphocytes and LDH were elevated in 17.7%, 7.7% and 60% of pts, respectively. Of all patients, 709 (32.8 %) pts had died. The median follow-up was 12.6 months, with a median survival of 61.8 months and the survival rate at 5 and 10 years of 51.2 % and 41.7 % respectively. PFs identified were: age, sex, zubrod, clinical stage, Hb, leukocytes, lymphocytes and LDH. The following table shows the p-value and hazard ratio (HR). The effect of continuous covariates in the log(HR) is non-linear. The cutoff points of highest (HR >1) match the clinically defined ones, which are: age >60yrs, Hb<12g/dl and LDH >240UI/L. Both leukocytes and lymphocytes have two higher risk breakpoints: leukocytes >3x103 and >10x103, lymphocytes <20% and >60%. Conclusions: PFs for OS in our group of pts were similar to other reports in NHL. Age, Hb, leukocytes, and lymphocytes are relevant to OS, which showed a nonlinear effect in the log (HR). [Table: see text]
Identification of ephrinB2 positive vessels in non-Hodgkin lymphoma subtypes.
Authors: Cohen Kenneth Stuart , Jamali Mina , Hyjek Elizabeth 
Published: March 2020

e19542 Background: Current anti-angiogenic therapies for tumors target signaling pathways such as VEGF. However, the role of alternative vascular pathways in tumor biology in general, and lymphoma biology specifically, are less well understood. Recently, the Eph receptor tyrosine kinase signaling pathway has emerged as a novel target for therapeutic inhibition. The EphB family member EphB4, and its reverse signaling ligand ephrinB2, are indispensible for developmental angiogenesis. Inhibition of ephrinB2 signaling results in impaired tumor growth in pre-clinical models. We therefore sought to determine if ephrinB2 is expressed in the microenvironment of human lymphomas and thereby represents a novel therapeutic target. Methods: We evaluated by immunohistochemistry on paraffin tissue sections expression of ephrinB2, CD34 (endothelial cells) and CD163 (macrophages) in LN biopsies from 12 cases of FL and 11 cases of DLBCL retrieved from the archives of the Department of Pathology at the University of Chicago (2000-2011). Eleven cases of follicular hyperplasia or quiescent LNs were used as controls (Cs). Slides were digitally scanned and examined both semi-quantitatively and by digital image analysis. Stained cells were quantified both in internal areas and at lymphoma-fat interfaces. Results: CD34+ microvessel densities were comparable between DLBCL and C groups but showed a significantly higher trend of interface angiogenic sprouts in FLs. Interface recruited CD163+ cell numbers were significantly higher in DLBCLs than in both FLs and Cs (p<0.0001). EphrinB2-expressing blood vessels were significantly increased in FLs but not in DLBCL. Conclusions: FLs demonstrate an increase in ephrinB2+/CD34+ vessels at the lymphoma-fat interface. In contrast, DLBCLs demonstrate no increase in ephrinB2+ vessels versus controls. However, DLBCLs were notable for increased recruitment of CD163+ macrophages at the tumor/host interface. These data represent the first analysis of ephrinB2 expression in human lymphomas and demonstrate heterogeneity between locations within a lymphoma and between histologic subtypes. Analysis of ephrinB2 in human lymphomas reveals marked heterogeneity in lymphoma microenvironmental domains.
Retrospective analysis of adjuvant chemotherapy for patients with soft tissue sarcomas at Washington University in St. Louis.
Authors: Schenone Aaron , Luo Jingqin , Montgomery Luke , Ley Jessica C. , Wildes Tanya Marya , Adkins Douglas , Van Tine Brian Andrew 
Published: March 2020

e21501 Background: Adjuvant chemotherapy for soft tissue sarcomas (STS) is controversial. We undertook a retrospective analysis to validate the Memorial Sloan Kettering Predictive Nomogram (MSKPN). We then independently analyzed low and high risk patients, as defined by MSKPN 4-year post operative probability of death > 30% for high grade patients to determine if high risk adjuvant chemotherapeutic patients had greater relapse free survival (RFS). Methods: A retrospective review was performed on all STS patients seen between 1/1/2000 and 5/1/10. Data collected included sex, age, race, city, stage, histology, primary lesion site and size, metastatic sites, response to therapy, radiologic response, and cause of death. The wilcoxon rank sum test was used to compare our predicted vs MSKPN predicted probability of death. Results: 170 subjects, 86 dead and 84 alive were assessed. 89 patients were classified as high risk, 17 treated by I/E, 2 by MAID, 3 by T&G and 67 untreated. 35 patients were treated with I/E and 124 received no adjuvant. We validated the MSKPN as predicted by age, histology, site, grade, depth and tumor size with low risk patients having a greater RFS (log rank test p=0.005) vs high risk. High risk patients’ age was significantly lower I/E v. untreated (mean=46 vs. 60.15, p=0.0044). Overall, patients treated with I/E had greater RFS (p=0.01). High risk adjuvant showed greater RFS vs untreated (log rank test p=0.015). Low risk adjuvant treated patients did not show greater RFS (p=0.346). Independent subtype analysis revealed leiomyosarcoma had the greatest RFS vs all other sub-types (p=0.011). High risk patients, with age accounted for, untreated patients have a hazard ratio of 4.67 (95% CI 1.19~18.35, p=0.027) relative to chemotherapy, indicating chemotherapeutic benefit for high risk patients. Conclusions: Presently there is insufficient and conflicting data for adjuvant therapy in the treatment of STS. Our retrospective data, within the limits of a retrospective analysis, demonstrates that our patient population behaves as predicted by the MSKPN. High risk patients given I/E have an overall RFS advantage. We propose a prospective risk stratified adjuvant therapy trial is warranted.
Mimics of gastrointestinal stromal tumors (GISTs): Implications for diagnosis and management—The Cambridge GIST Study Group (CGSG) experience.
Authors: Wong Han Hsi , Chengal Rajani , Hardwick Richard , Horan Gail , Hatcher Helen , Earl Helena Margaret , Pursglove Stephanie , Bulusu Venkata Ramesh 
Published: March 2020

e21503 Background: Historically, GISTs were often misdiagnosed as other tumours. However, with the increasing awareness of GISTs, one needs to be careful in confirming the diagnosis since other tumours can simulate GISTs on endoscopy/imaging/histology. We report our 8 year experience of GIST mimics from the CGSG database. Methods: 250 cases discussed in the specialist multidisciplinary meeting from 2004 – 2012 were reviewed. Tumours initially suspected to be GISTs but turned out to be other tumours were included in this analysis. Patient demographics, endoscopic, imaging and histological features were analysed in 41 GIST mimics. Central review by specialist histopathologist was undertaken with immunohistochemical and molecular analysis to differentiate these tumours from GISTs. Results: GIST mimics N= 41. Median age 56 years (range 11 – 82 years), male:female ratio 1:1. Median size 8 cm (range 1.9 – 30 cm). Site of origin of tumours: stomach 34%, oesophagus/junction 15%, mesentery 12%, small bowel 10%, colon 5%, retroperitoneum 5%, pancreas 5%, liver 2% and indeterminate site of origin 12%. Suspicion of GIST was raised from imaging (46%), endoscopy (41%) and histology (39%). The histological subtypes of GIST mimics are summarised in the Table. Conclusions: Many benign and malignant tumours do mimic GISTs on imaging/endoscopy or histology. The diagnosis of GISTs should be made by a specialist multidisciplinary team with experience in imaging and histopathology. Distinguishing GISTs from their mimics is of critical importance both for prognosis and management. [Table: see text]
Generation of a new xenogenic transplantation model for the analysis of undifferentiated pleomorphic sarcoma: NOS in mice.
Authors: Wehler Thomas , Becker Marc , Grebe Nadine , Theobald Matthias , Rommens Pol Maria , Proschek Dirk , Graf Claudine 
Published: March 2020

e21505 Background: Undifferentiated pleomorphic sarcoma, NOS (not otherwise specified) formerly known as MFH comprise about 15-20% of all soft tissue sarcomas (STS) in adults. This kind of sarcoma is characterized by low response to radiation or chemotherapy. Thus, surgery with the aim of R0-resection is still the cornerstone for a curative treatment regimen. However, surgery is not always possible. In the recent past, many efforts have been undertaken to refine chemotherapeutic options and to develop new drugs for targeted therapies, such as mTOR-inhibtors or tyrosine kinase inhibitors. Yet, the hoped break through is still lacking. In addition, the further development of entity-based new drugs is difficult due to the low incidence of STS and suitable reproducible animal models. Here, we present a new xenogenic transplantation model of a pleomorphic sarcoma in mice. Methods: After intraoperative resection of the sarcoma, a sarcoma-derived cell line was established. These cultured cells were injected s.c. (1x10E6 cells) in immunocompromised NOD/SCID γc-/- mice and in humanized NOD/SCID γc-/- mice. Results: Tumor growth was reproducibly seen after four to six weeks. When resected after 12 weeks, the xenogenic tumor presented the same histological and morphological characteristics as the original tumor. Tumor infiltrating lymphocytes were detected by immunhistochemical staining. Conclusions: This new xenogenic transplantation model can serve as a basis for the evaluation of manifold questions within the fields of oncology, tumor genetics and tumor immunology.
Multimodality management of synovial sarcoma: Review of single institutional experience.
Authors: Manjunath N.M.L. , Deo S. V. S. , Shukla N. K. , Bakhshi Sameer , Sharma Dayanand 
Published: March 2020

e21506 Background: Soft tissue sarcomas (STS) are rare malignancies constituting 1% of all solid tumors. Synovial sarcoma (SS) constitutes 5-10% of all sarcomas. Histopathologically SS is classified as Monophasic, Biphasic and Poorly differentiated varieties and majority are high grade. There is paucity of literature pertaining to SS from developing countries. Methods: Study population was selected from a prospectively maintained STS database at the department of Surgical Oncology, Dr BRAIRCH, AIIMS. All patients with pathological diagnosis of SS were included for the analysis. Results: A total of 446 patients of STS were treated from 1995 to 2009 and 80 cases of pathologically proven SS were selected. Median age at diagnosis was 33 years. There were 53 males (66.3%) and 27 females (33.8%). Most common site was proximal lower limb, majority involving thigh. Sixty one patients presented with prior inadequate interventions including intralesional excision or marginal excision. Sixty seven cases had tumors more than 5 cm in size and 27 more than 10 cm. Lymph nodes were seen in 9 patients (11.3%) but only 4 showed pathological involvement. According to MSKCC staging 83% had stage III disease and stage I and II constituted 10.5%. Ten patients had metastasis at presentation and all of them had lung metastasis. Among the extremity sarcoma, 35 (43.8%) patients had limb salvage surgery and the rest required amputations due to advanced nature of disease. Overall 15% of cases required reconstruction and only 6 had positive margin. Postoperatively 35 patients received radiotherapy and 52 received chemotherapy (Adriamycin Ifosamide based). At a median follow up of 59 months,10 patients had local recurrence and 34 (42.5%) patients had systemic relapse mainly in the lungs (27 patients). At last follow up, 58 patients were alive of which 44 were disease free. The overall 5 year survival was 52%. Conclusions: SS is a rare tumor involving younger age group. Due to lack of awareness among patients and physician, majority present with suboptimal surgical intervention or advanced stage in developing countries resulting in a low limb salvage rate. Most common site of relapse is lung despite multimodality management resulting in a modest 5-year survival of 52%.
Efficacy of trabectedin for advanced soft tissue sarcoma (ASTS): A retrospective single center analysis.
Authors: Martinez-Trufero Javier , Pajares Isabel , Hernandez Garcia Alba , Cebollero Ana , Calera Lourdes , Anton Antonio 
Published: March 2020

e21509 Background: Trabectedin (Yondelis) is the first marine-derived antineoplastic drug approved in Europe for the treatment of patients with recurrent ASTS or for patients unsuited to receive anthracyclines and ifosfamide. We retrospectively analyzed patients with ASTS treated with trabectedin from Nov. 2006 to April 2012. Methods: Trabectedin was given at the approved dose of 1.5 mg/m2as a 24-h infusion every 3 weeks. An analysis of response rate, time to progression (TTP) and overall survival (OS) and univariate analyses of prognostic factors were performed. Results: Overall,39 patients (24 men) with mostly high-grade (n=29) ASTS with a median age of 57 years (range 20-81) were analyzed. Most had L-type STS (leiomyosarcoma n=10; liposarcoma n=3), undifferentiated pleomorphic sarcoma (n=11), sarcoma NOS (n=5), or synovial STS (n=2). Eight had one of 6 very rare STS. At baseline patients had metastatic (n=21), bulky (n=4) or metastatic/bulky (n=14) disease and were pretreated with a median of 2 prior chemotherapy lines (range: 0-3; 4 patients received adjuvant chemotherapy only), including anthracycline-based chemotherapy (n=30), gemcitabine plus dacarbazine (GEM-DTIC; n=18), other (n=20). Patients received a median of 4 trabectedin cycles (range 1-34). Among 37 evaluable patients best responses as per RECIST were partial response (PR, n=7), stable disease (SD >3 months, n=9, 5 had SD >6 months) and disease progression (n=19), and 5 patients had a decrease in tumor density. Responses to trabectedin and GEM-DTIC did not exclude responses to the other regimen suggesting the feasibility of sequential treatment. After a median follow-up of 9.37 months, median TTP and OS were 4.4 months (95% CI: 3.5-5.4) and 9.7 months (95% CI: 4.5-14.9), respectively. Univariate analyses identified low/medium-grade STS and growth modulation index >1.13 as favorable prognostic factors for TTP, and retroperitoneal/visceral localization, L-type and rare STS and low/medium-grade STS for OS. Conclusions: The results of this real-life retrospective analysis confirmed the findings of previous trials showing that trabectedin is active drug for ASTS.
Gastrointestinal stromal tumors: Institute of Oncology—Dr. “Luis Razetti” experience, Caracas, Venezuela.
Authors: Chirinos Luis , Fuentes Maria Belen , Perez Maria Angelina , Gotera Gustavo , Parra Jesus Felipe , Garcia Sebastian Cristina 
Published: March 2020

e21512 Background: Gastrointestinal Stromal Tumors are a heterogeneous group of tumors with clinical features and specific genetic alterations, which represent 1-3% of all gastrointestinal cancers. Imatinib, is the standard treatment in advanced and localized disease, and has demonstrated benefit in overall survival, progression free survival and disease free survival. Methods: The primary end point was to evaluate overall survival in patients with locally advanced, metastatic and early stage GIST treated with Imatinib; secondary end points were to evaluate disease-free survival and progression free survival. We included 34 patients with GIST treated between January 2005 and December 2011. Results: The most affected gender was male (55.88%), the average age was 51-60 years (26.47%), and most had localized disease at diagnosis (73.52%), mainly in the stomach (52.94%). As for the primary treatment, 25 underwent surgery (73.5%), applying adjuvant Imatinib in 18 patients (75%).The OS and DFS was higher in patients with localized disease compared with age (p = 0.0001 respectively). Regarding the use of adjuvant Imatinib, it produced clinical benefit in DFS and OS of 50 and 60 months respectively, regardless of risk. In patients with advanced or metastatic disease Imatinib was associated with higher PFS (p = 0.055) and OS (p = 0.1120). Relapses occurred in 24% of patients regardless of risk and the use of Imatinib. Conclusions: In our study we concluded that radical surgery and the use of Imatinib in GIST patients produce important clinical benefits which translate into higher survival rates.