bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity and tolerability of cisplatin (CDDP) and fotemustine (FTM) in non-small cell lung cancer (NSCLC) patients (PTS) with brain metastases (BM): A multicentric phase II study of the Gruppo Oncologico dell’Italia Meridionale (GOIM)
Authors: Galetta D. , Gebbia V. , Ferraù F. , Carrozza F. , Cigolari S. , Russo P. , Calista F. , Adamo V. , Colucci G. 
Published: August 2020

e19085 Background: More than 50% of BM occurs in advanced NSCLC. In most cases BM are multiple and their standard therapy is whole-brain radiation therapy (WBRT) since the role of systemic therapies for is still a matter for investigation due to concerns on the drugs ability cross the blood brain barrier (BBB). FTM is a nitrosourea able to cross BBB and CDDP remains the backbone for medical treatment of NSCLC. Methods: Pts with advanced NSCLC, ECOG PS 0–1 and multiple BM were treated with 2 cycles of FTM 80 mg/m2 d1,8 and CDDP 80 mg/m2 d1 q3 wks followed by WBRT 30 Gy/3 Gy daily; radiological response using Recist Criteria were analysed before WBRT to assess the role of FTM/CDDP both for cranial and extracranial disease. Pts with disease control (DC) received further CT up to 6 cycles. Barthel ADL Index was administered every 2 cycles. The trial has a two step design according to Simon: 29 pts were required to verify if FTM/CDDP was able to achieve a >25% response rate both for cranial and extracranial disease (step 1), and if this was true further pts had to be enrolled up to 81 pts (step 2). Results: At first evaluation 4/29 pts were excluded from the study (2 not treated/ 1 never included/1 not eligible). Therefore patient's demographics were: median age 61 (range 48–73), M/F 16/9, adeno 11, squamous 5, large cell 2, nos 7; PS 0/1: 1/14, Barthel Index median value at the starting point 20 (13–20). Overall 3/25 (12%) partial responses were observed with 9 (36%) stable diseases and 13 (52%) progressions of disease. These data did not satisfy the pre-planned hypothesis and the study was stopped at the first step. Before WBRT after the first 2 CT cycles 13/25 pts (48%) had a systemic DC in contrast with 15/25 pts (60%) with brain tumour DC. WBRT seemed not useful to further modify the results of CT. CT was relatively well tolerated with asthenia as the most relevant specific toxicity while the hematological toxicity was mild. Conclusions: CDDP and FTM combined with WBRT could represent a therapeutic option for patients with NSCLC even if the global therapeutic index was not satisfactory. Further studies evaluating the combination of systemic treatments with WBRT are warranted. No significant financial relationships to disclose.
First-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) by gefitinib
Authors: Moiseyenko V. , Procenko S. A. , Levchenko E. V. , Barchuk A. S. , Matsko D. E. , Moiseyenko F. V. , Ivantsov A. O. , Iyevleva A. G. , Mitiushkina N. V. , Imyanitov E. N. 
Published: August 2020

e19088 Background: Gefitinib shows outstandingly high rates of clinical benefit in NSCLC pts with EGFR mutation and is better tolerable than conventional chemotherapy, therefore its consideration for the upfront treatment is warranted. Methods: 21 chemonaive pts with inoperable NSCLC were selected based on the presence of EGFR mutation in the tumor DNA (16 exon 19 deletions and 5 T858G substitutions). All cases were adenocarcinomas; median age: 60 years (range: 36 - 81 years); males/females: 6/15; ECOG PS 0/1/2/3: 4/10/6/1. Gefitinib was administered at conventional dose 250 mg/d. Results: The overall disease control rate was 95% (CR: 2/21; PR: 11/21; SD: 7/21). Complete responses were observed only in tumors with exon 19 deletion, whereas the only patient with disease progression had codon 858 substitution. Grade III toxicity occurred only in 3 pts (2: skin rash; 1: diarrhea). Time to disease progression ranged from 2+ to 18 months. 3 pts achieved an operable status of the disease upon the treatment, and therefore were subjected to surgical intervention followed by adjuvant gefitinib therapy. Conclusions: Gefitinib may be considered as the treatment of choice for chemonaive EGFR mutation-containing inoperable NSCLC. No significant financial relationships to disclose.
Survival of patients (pts) with advanced lung adenocarcinoma (ALA) treated in four hospitals from Bogotá D.C., Colombia, and report of a novel alteration in the epidermal growth factor receptor (EGFR) (ONCOLGroup study)
Authors: Otero J. M. , Cardona A. F. , Carrasco-Chaumel E. , Carranza H. , Vargas C. , Carlos C. , Diana T. , Ludovic R. , Reguart N. , Cuello M. 
Published: August 2020

e19097 Background: This study included 147 ALA pts treated between 2000 and 2007. Overall response rates (ORR), clinical benefit (CB), time to progression (TTP) and overall survival (OS) were estimated. EGFR E19 deletions were studied by length analysis fluorescently and the exon 21 L858R mutation by PCR Taqman assay. Results: Mean age was 66±12.8 years. Seventy- eight pts were women, 40% had never been exposed to tobacco smoke and PS was ≥70% in 119 pts. The brain was the dominant site for metastasis (38%) followed by the lungs (38%). Sixty-nine percent of the pts received a platinum doublet as first-line intervention and 32 pts (21.8%) had received erlotinib (E) as part of their treatment. Response to first-line treatment was available in 110 pts; ORR was 28%, CB 39% and TTP 4.2 mo. (range, 0.2–11). Second-line therapy was administered to 46 pts; ORR was 8%, CB 25% and TTP 3.7 mo. (range, 0.4–12). Twenty pts received third-line therapy, with an ORR of 35%, CB 50% and a TTP 3.9 mo. (range, 1.0–5.7). Median OS was 10.1 mo. (range, 6.3–19) and the PS, absence of tobacco exposure, and administration of E, positively influenced this outcome. EGFR mutational profile was assessed in 6 pts; 3 pts presented mutations in E19, one a 5-nucleotide deletion (E746_A750) and 2 pts had a 3 serine-rich nucleotide insertion (L747_S75) which has not been previously reported. The first patient had a partial response, and the last two, had survival greater than 16-mo. Conclusions: Outcomes for pts suffering from ALA in Colombia are similar to those described in other Latin American countries. Three pts with EGFR alterations were identified in this cohort; two presented a non- described change in E19 which may have corresponded to a novel alteration in our region, with possible increased sensitivity to E. No significant financial relationships to disclose.
Pemetrexed versus gefitinib versus erlotinib in previously treated non-small cell lung cancer by retrospective analysis
Authors: Cho E. , Hong J. , Kyung S. , Kim Y. , Shim S. , Park J. , Jung S. , Park J. , Shin D. , Lee J. 
Published: August 2020

e19103 Background: The standards in 2nd-line therapy with advanced non-small cell lung cancer (NSCLC) were erlotinib or pemetrexed as well as docetaxel. To evaluate the efficacies and safeties of pemetrexed, gefitinib, and erlotinib in previously treated NSCLC we analyzed the datas retrospectively. Methods: Eligible patents were 1) histologically confirmed pretreated advanced (stage IIIB or IV) NSCLC, 2) with at least one measurable lesion, 3) age over 18 years, 4) performance status (PS) 0–2, and 5) should never experience other two drugs as previous therapy. Patients of pemetrexed group received IV infusion of 500mg/m2 pemetrexed mixed with normal saline every 3 weeks with vitamin B12 and folate supplementation. Patients of gefitinib group received gefitinib 250mg PO daily and of erlotinib took erlotinib 150mg PO daily. Cycles of IV pemetrexed or taking PO drugs were continued until disease progression or unacceptable toxicity. Results: we analyzed 57 patients (pemetrexed; 20, gefitnib; 20, and erlotinib; 17). The response rates were 5.3%, 25.0%, and 12.5% (P=0.22), and the disease control rate were 5.3%, 40.0%, and 50.0% respectively (P<0.01). Median progression-free survival (PFS) of pemetrexed, gefitinib, and erlotinib were 1.7, 3.5 and 4.4 months (P<0.01) and median overall survival (OS) were 5.6, 21.8 and 21.5 months respectively (P=0.04). In subgroup analysis, patients with non-squamous carcinoma, smokers and good PS (0 or 1) showed longer PFS and OS in gefitinib and erlotinib compared with in pemetrexed. All of these agents showed mild and tolerable toxicity. Conclusions: In retrospective analysis, the patients with gefitinib or erlotinib had longer PFS and OS than pemetrexed, eventhough there was no significant difference for response rate in three group. These results have to confirm by large randomized prospective study because the sample size was small and it was not randomized. No significant financial relationships to disclose.
The use of single-fraction radiation therapy in cutaneous T-cell lymphoma
Authors: Babbo A. M. , Chokshi M. , Rademaker A. , Mittal B. 
Published: August 2020

e19505 Background: Primary cutaneous lymphomas occur in 0.5 to 1 per 100,000 people every year in developed countries. Less than 1,000 cases of Mycosis Fungoides are diagnosed each year in the United States, with approximately 3 cases per 1,000,000 per year. Cutaneous T-cell lymphomas are responsive to radiation therapy, and local radiation therapy, total skin electron beam therapy, phototherapy (with UVB or PUVA), chemotherapy agents (nitrogen mustards, BCNU), retinoids, and steroids have all been used with varying degrees of success. Methods: This is a retrospective review of all cases of histology-proven cutaneous T-cell lymphoma treated with single-fraction radiation therapy at Northwestern Memorial Hospital in the Department of Radiation Oncology since 1990. We looked at response to treatment and local control. We reviewed the charts of 67 patients with cutaneous T-cell lymphoma, of which 40 patients and a total of 130 sites of disease received single-fraction radiation therapy and had available follow-up data. Results: Of the 130 lesions receiving a single-fraction of radiation, 86 (66%) received 800cGy in 1 fraction and 38 (29%) received 700cGy. 4 patients (3%) received 750cGy, 1 (<1%) received 550cGy and 1 (<1%) received 500cGy. Patients were treated with electron energies ranging from 6–18 MeV or photon energies ranging from 4–10 MV. Out of 130 lesions, 119 (92%) achieved a complete response (CR) to single-fraction radiation and 11 (8%) achieved a partial response (PR). There were 2 sites of relapse out of 130 treated sites, involving 2 patients. The median follow-up time was 4 months, mean follow-up time was 14 months, and 44% of patients had greater than 6 months of follow-up. Conclusions: This review of the experience at our institution since 1990 shows single-fraction radiation therapy to be an effective treatment for cutaneous T-cell lymphoma, with high response rates and very low relapse rates. No significant financial relationships to disclose.
Natural history of multiple myeloma (MM) relapsing after autologous stem cell transplantation (ASCT)
Authors: Madan S. , Kumar S. , Lacy M. Q. , Dispenzieri A. , Hayman S. R. , Buadi F. K. , Dingli D. , Rajkumar S. V. , Gertz M. A. 
Published: August 2020

e19513 Background: The outcome of patients with MM relapsing after ASCT used early in the disease course or after failure of initial therapy, is not well defined. We undertook this study to understand treatment approaches for patients relapsing after single ASCT. Methods: Patients relapsing after single ASCT were identified from a prospectively maintained database and relevant clinical data were extracted from medical records. Relapse and treatment responses were according to IMWG Uniform Response Criteria. Patients relapsing between Jan 2000 and 2008 were included in order to capture a recent cohort contemporaneous to availability of novel drugs. Results: We studied 487 patients who had relapsed following a single ASCT, of whom 351 (72%) had an early SCT (≤ 12 mos from diagnosis). The median estimated follow up for all patients was 27 mos, 50 mos and 69 mos from relapse, SCT and diagnosis respectively. The median overall survival (OS) from the time of relapse was 30 mos for the early SCT group and 21 months for the late SCT group. The median time to relapse following transplant was 15 mos (3–119) among early SCT group and 12 mos (3–76) among the late SCT group. Longer time to relapse as well as longer time from relapse to initiation of therapy were independent predictors of better outcome. Among the early group, nearly a third of the patients achieved a PR or better to first salvage therapy (Table), with another third achieving stable disease and 25% of patients did not have response data. The median progression free survival for the first salvage regimen was 8 mos; 18 mos for those with PR or better and 5 mos for those with SD as the best response. Data on the regimen 2, 3, 4, 5, and 6 were available for 211, 133, 84, 53 and 28 patients respectively. As expected, the response rates and the response duration decreased with increasing number of relapses. Conclusions: Patients relapsing after ASCT can obtain prolonged response duration with the currently available treatments. Those with a durable response to transplant and those not requiring initiation of therapy for long periods after disease relapse have favorable disease biology and have prolonged survival after relapse. The natural history of the disease provides a valuable benchmark for evaluation of newer treatment approaches. No significant financial relationships to disclose.
DNA methylation status of Smurf2 promoter in patients with multiple myeloma
Authors: Hatzimichael E. , Dasoula A. , Stebbing J. , Dranitsaris G. , Crook T. , Bourantas K. 
Published: August 2020

e19537 Background: Multiple myeloma (MM) is an incurable interleukin (IL)-6 dependent plasma-cell malignancy. Transforming growth factor-β (TGF-β) is the major inducer of IL-6 secretion by bone marrow stromal cells. The signaling responses to TGF-b are mediated by the Smad proteins. The Smurf2 gene (Smad ubiqitiniation regulatory factor 2) encodes a Smad-specific E3 ubiquitin ligase and targets Smad2 and Smad3 for proteasome-dependent degradation. Methods: Bone marrow samples from individuals with MM were obtained at diagnosis and in 5 cases at disease progression as well. Genomic DNA was isolated and bisulphite modification was performed using commercially available kits. The methylation-specific polymerase chain reaction was employed to study the methylation status of the CpG island. Logistic regression analysis was used to measure the association between gene methylation and the development of advanced disease (DS≥ II), extramedullary disease, bone disease, anemia (Hb 10 mg/dl), serum albumin and beta 2 microglobulin levels. Results: We analysed the methylation of Smurf2 in 45 cases of MM (24 male, 21 female, mean age 66.4 years). No sample from the control population was found methylated. The Smurf2 gene promoter was found to be methylated in 11/45 MM patients (24%). Interesting trends were noted where patients with methylated Smurf2 promoter had an increased risk of death (HR = 1.3; p = 0.68), anemia (OR=2.1, p=0.2) and advanced stage (OR=1.3, p=0.6) and a reduced risk of extramedullary disease (OR= 0.2, p=0.2). No association was found between Smurf2 methylation status and bone lytic lesions, serum albumin levels or beta-2 microglobulin levels. Conclusions: Interesting associations between Smurf2 methylation and some relevant clinical parameters in patients with MM were suggested by the data. These findings warrant further evaluation in a larger sample of patients in order to enhance our statistical power and better define the prognostic and clinical value of Smurf2 methylation in MM. No significant financial relationships to disclose.
Neutrophil toxicity and primary prophylaxis in diffuse large B cell lymphoma treated with R-CHOP
Authors: Naqi N. , Khatak J. 
Published: August 2020

e19548 Background: Three weekly R-CHOP therapy is regarded as standard treatment in advanced stage Diffuse Large B Cell Lymphoma (DLBCL) patients with low to intermediate-risk International prognostic index (IPI). This regimen is associated with intermediate risk (10–20%) of febrile neutropenia. Primary prophylaxis with colony-stimulating factor (CSFs) is therefore not recommended except in the presence of high risk factors as defined in the National Comprehensive Cancer Center Network guidelines for use of myeloid growth factors v.1.2008. It is however well realized that a significant number of good risk patients will still develop significant neutrophil toxicity. Methods: This observational study was conducted at Oncology department Combined Military Hospital, Rawalpindi, on fifty good risk patients of advanced stage DLBCL, treated with R-CHOP regimen without primary CSFs prophylaxis. NCI Common Toxicity Criteria version 3.0 was used for grading toxicity and significant neutrophil toxicity was defined as Grade 4 neutropenia between day 7 and 10 post therapy, febrile neutropenia and Grade 2 or more neutrophil toxicity persisting on day 1 of next cycle. Good risk patients were recruited by the following exclusion criteria: WHO Performance status scale 4, concurrent immunosuppressive drug therapy, abnormal hepatic or renal functions and inadequate hematological values. Results: 10(20%) patients, developed significant neutrophil toxicity. In this group 7(70%) had grade 4 neutropenia and 3(30%) patients developed febrile neutropenia. 8(80%) of these patients developing significant toxicity had WHO Performance scale ≥ 2. 2(20%) patients developing Grade 4 toxicity between days 7 and 10 post therapy had good performance status (0 or 1) and toxicity resolved by next cycle without getting complicated to febrile neutropenia. Conclusions: Performance status in terms of scale has not been defined in the high risk factors for developing febrile neutropenia in the NCCN guidelines on myeloid growth factors use. We observed that DLBCL patients with WHO performance status scale ≥ 2 treated with R-CHOP therapy at 3 weekly intervals are at greatest risk for developing significant neutrophil toxicity and febrile neutropenia. No significant financial relationships to disclose.
A study of the prevalence and type of anemia in lymphoid malignancies
Authors: Ghosh J. , Kumar L. , Saxena R. , Raina V. , Sharma A. , Gupta R. , Vivekanandhan S. , Sreenivas V. , Verma R. 
Published: August 2020

e19556 Background: Anemia is a common and serious problem in patients with lymphoid malignancy. Hence there was need to analyze the prevalence of anemia in our patient population and evaluate its cause for optimal management. Methods: Newly diagnosed patients of lymphoid malignancy- non Hodgkins lymphoma (NHL), Hodgkins lymphoma (HL), and chronic lymphocytic leukemia (CLL) aged more than 15 years without renal failure and who had not received blood transfusion, iron, folic acid or vitamin B complex in the last 2 weeks were analyzed. 316 patients were screened for the prevalence of anemia. Of the anemic patients (hemoglobin <11gm/dl), 46 were studied for the type of anemia. These patients underwent the following investigations -complete hemogram with RBC indices, hematocrit, reticulocyte count, peripheral blood smear (PBS) examination, direct Coombs test (DCT), bone marrow (BM) aspiration and biopsy, S. iron (SI), S. ferritin (SF), total iron binding capacity (TIBC), percentage saturation (psat), S. Vitamin B12 and Folic acid levels. Anemia was categorized as due to either autoimmune hemolytic anemia (AIHA)-DCT positive with evidence of hemolysis on PBS, B12 and folate deficiency (<200 pgm/ml and < 4ngm/ml respectively), iron deficiency anemia (IDA)- psat <20% and SF315μgm/dl, anemia of chronic disease (ACD)-psat200μgm/L, a combination of IDA and ACD -psat <20%, SF -30–200 with TIBC ≤315 μgm/dl. Results: The prevalence of anemia in patients with lymphoid malignancy was 42.41% (134 /316, 95% CI-36.96% -47.85%). It was multifactorial in 39.13% (18/46) patients. ACD was the most common cause of anemia present in 71.74% (33/46) patients. This was followed by nutritional anemia (iron,B12 and folate deficiency) in 47.83% (22/46) and AIHA in 10.87% (5/46) of patients. Conclusions: Although anemia of chronic disease is the most common cause of anemia in patients with lymphoid malignancy, it is multifactorial in a large number of patients and hence it is important to rule out other causes of anemia like nutritional and AIHA in these patients. No significant financial relationships to disclose.
Ipilimumab in the common daily practice: Feasibility, safety, and efficacy in heavily pretreated metastatic melanoma patients
Authors: Di Giacomo A. , Danielli R. , Calabrò L. , Guidoboni M. , Miracco C. , Biagioli M. , Mazzei M. , Altomonte M. , Maio M. 
Published: August 2020

e20002 Background: Effective anti-tumor responses are being observed in metastatic melanoma (MM) patients (pts) with the anti-CTLA-4 antibody Ipilimumab (Ipi) in clinical trials; however no data support the feasibility and clinical effectiveness of Ipi use in the daily practice. We report a single Institution experience utilizing Ipi within a compassionate program for MM pts. Methods: 27 stage III (2) or IV (25) pts (14 males, 13 females), median age 55 (23–77) years, ECOG performance status 0- 1, with MM (23 cutaneous, 3 uveal, 1 mucosal) progressing to 3 median (1–5) systemic therapies for metastatic disease received Ipi. Eight pts had evidence (6) or history (2) of brain metastases and 11 elevated (>1x upper limit of normal [ULN]) LDH. In the induction phase (IF) pts received Ipi (10 mg/kg i.v.) q3 weeks (wks) x 4 cycles; after a 12 wks rest treatment was repeated q12 wks in the maintenance phase (MF). Tumor assessment (TA) per modified World Health Organization criteria was performed at baseline, week (wk) 12 (±2) and wk 24, then every 12 wks. Adverse Events (AE) and immune related AE (irAE) were collected according to Common Terminology Criteria for Adverse Events version 3.0. Results: All pts received at least one Ipi dose, and 18/27 completed the IF. Of the remaining 9 pts, 4 are completing the IF and 5 were withdrawn for AE severity (3 pts) or disease progression (2 pts). Eight pts entered the MF. TA at wk 12 showed partial response (PR) in 1/18 or stable disease (SD) in 5/18 pts. TA at wk 24 showed PR and SD in 3/8 and 5/8 pts, respectively, with an ongoing clinical benefit (SD + PR + CR) of 34% (8/23 pts); these pts are still on treatment. Slow, steady declines in tumor volume and appearance of new lesions with subsequent shrinking of total tumor burden has been observed. One patient had Grade 3 AE (myocardial infarction) and 2 pts had Grade 3 irAE (diarrhoea). Excluding pts who are in IF, to date median overall survival is 27 wks (19–39). Conclusions: Ipi treatment is feasible, safe and clinically effective also in the common daily practice and in heavily pretreated, progressing, MM pts. A sizable proportion of these pts experiences durable clinical benefit. No significant financial relationships to disclose.