bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is symptom improvement in patients with small cell lung cancer (SCLC) associated with clinical response? An analysis using the Patient Symptom Assessment Lung Cancer (PSALC) scale in a randomized trial comparing oral topotecan (OT) with best supportive care (BSC)
Authors: O'Brien M. E. , Duh M. , Chen L. , Antras L. , Neary M. , Dharan B. , Gralla R. J. 
Published: March 2020

7725 Background: SCLC is a highly symptomatic disease with poor survival in prior treated patients. To evaluate the role of chemotherapy, a recent multicenter trial randomized 141 patients with prior treatment to receive either OT + BSC or BSC only. This was the first trial to use a BSC control group in SCLC while evaluating survival, response and symptoms. Survival data were reported (O'Brien et al JCO 2006; median survival of 25.9 weeks on OT + BSC vs 13.9 weeks on BSC, p = 0.01). 51% on OT had “disease control” (partial response [PR] + stable disease [SD]); no patient on BSC was reported to have a major response, although response was not an endpoint for this group. Trials have shown that those with progressive disease have the most symptom worsening, as occurred in this trial. The objective of this analysis is to determine if patients with PR report greater symptom relief than those with SD, in that SD can reflect a more indolent course in some patients while PR is due to treatment effect only. Methods: We used the investigators evaluation of response (PR or SD) and analyzed these groups by the patients’ scoring of their symptoms using the PSALC instrument which evaluates 9 SCLC symptoms, in the 71 patients on the OT + BSC arm. Results: Patients with lower ECOG PS at baseline reported more severe symptoms (higher PSALC score). Mean changes in PSALC score from baseline are shown in the Table and demonstrate an association between tumor response and decrease in symptoms. Conclusions: Patients who achieved a major response on OT treatment reported significantly better symptom control than those whose best response was SD. This indicates that in addition to a survival benefit, treatment with this chemotherapy can aid in symptom control. While the small number of patients limits the strength of the conclusions, this trial represents the largest BSC controlled study in SCLC. No significant financial relationships to disclose. [Table: see text]
Phase II study of short course CHOP-rituximab (R) followed by ibritumomab tiuxetan (IT) as first-line treatment for follicular lymphoma (FL)
Authors: Jankowitz R. C. , Foon K. A. , DeMonaco N. A. , Osborn J. , Wu M. , Evans T. , Swerdlow S. H. , Joyce J. , Land S. , Jacobs S. A. 
Published: March 2020

8005 Background: Therapy with CHOP-R and radioimmunotherapy (RIT) is a promising treatment for untreated FL. Press reports complete responses (CR) of 69% in FL patients (pts.) with 6 cycles of CHOP followed by I-131 tositumomab. We report efficacy and safety using 3 cycles of CHOP-R followed by IT and extended R. Methods: Eligibility criteria include symptomatic or grade 3 untreated FL. 60 pts. have been accrued and 47 evaluated. The treatment consists of two phases: CHOP-R for 3 cycles followed by IT. One week after IT, pts receive R weekly × 4. Bone marrow (BM) biopsies and fusion PET-CT scans are obtained at baseline, after CHOP-R, and 12 weeks post RIT. The primary endpoint is CR rate. CR requires a neg. PET scan and conventional Working Group criteria. Results: Toxicity data are available for 47 pts of median age 56 (range, 39–78), 44 of whom completed both phases of therapy and are evaluated for response. Characteristics and CR rates after IT are shown: 3 pts. did not receive RIT (1 second malignancy, 1 non-compliance, 1 septic death). Of the 44, CR after CHOP-R is 41%. After IT, CR improved to 89%. Of the 5 pts who did not achieve CR, 3 had neg. PET scans (2 with PR, 1 with SD by CT), and 2 had residual disease by PET with PR by CT. At a mean follow-up of 16 months (range, 6–33 months), there are 4 relapses: 3 who achieved CR by PET-CT, 1 with PR by PET-CT. Toxicity was predominantly myelosuppression. There was 1 episode of febrile neutropenia after RIT. Conclusions: 3 cycles of CHOP-R followed by IT and R achieve a high CR in previously-untreated pts. with FL. Addition of RIT increased CR from 41% to 89%. Data will be presented on the affect of bulky disease, positive BM, grade 2 or 3 histology, and high FLIPI score on CR. Further follow-up is necessary to evaluate response duration and determine whether there is a correlation with early or late CR. [Table: see text] [Table: see text]
Maintenance rituximab (MR) compared to observation (OBS) after R-CHOP or CHOP in older patients (pts) with diffuse large B-cell lymphoma (DLBCL): An Intergroup E4494/C9793 update
Authors: Morrison V. A. , Weller E. A. , Habermann T. M. , Cassileth P. A. , Cohn J. B. , Gascoyne R. D. , Woda B. , Fisher R. I. , Peterson B. A. , Horning S. J. 
Published: March 2020

8011 Background: Maintenance therapy is generally not used in treatment of DLBCL. However, older pts are a unique group in which to study this approach, due to poorer outcome. Methods: As part of intergroup trial E4494/C9793, 415 pts >= 60 years (yr) of age with DLBCL who responded to induction therapy with CHOP or R-CHOP were randomized to MR (rituximab, 375 mg/m2 weekly {wk} X 4 every 6 months for 2 yr) starting 4 wk after the last chemotherapy (n=207) or observation (OBS, n=208) in a prospective 2 × 2 randomized trial design (J Clin Oncol 2006;24:3121). Impact of MR on failure-free survival (FFS) was the primary objective, and impact on time to failure (TTF) and overall survival (OS) were secondary objectives. All p-values are two-sided. Results: Results are presented for 352 centrally reviewed evaluable pts, with a median follow-up after maintenance randomization of 5.5 yr. All results were similar for the intent-to-treat population. Baseline characteristics and response to induction therapy are balanced among the CHOP/R-CHOP pts. At 6 yr, FFS was 46% for those pt who received MR and 36% for the OBS cohort (p=0.005, hazard rate {HR} 0.64); 6-yr OS was 62% for MR and 64% for OBS (p=0.83, HR 0.96). Outcome was also examined in the four treatment subgroups. The 6-yr FFS were: CHOP+MR 44%, CHOP+OBS 35%, R-CHOP+MR 47%, and R- CHOP+OBS 40%. No differences in 6-yr OS were observed according to maintenance randomization following CHOP (57% MR vs 55% OBS) or R-CHOP (67% MR and 72% OBS). Median TTF after maintenance randomization following CHOP+MR was 5.2 yr vs 1.6 yr for CHOP-OBS (p=0.0004), and following R-CHOP+MR was 5.6 yr vs 5.4 yr with R-CHOP-OBS (p=0.50). Proportionately more of the treatment failures occurred within 2 yr after CHOP+OBS (85%) compared to CHOP+MR (61%), p=0.01. In contrast, the proportion of failures within 2 yr was similar for R- CHOP+OBS (47%) and R-CHOP+MR (53%), p=NS. Conclusions: MR after CHOP, but not after R-CHOP, significantly prolongs TTF, but fails to prolong OS, possibly due to a delayed pattern of relapse and/or the efficacy of rituximab in the salvage setting. As 6-yr FFS declined to <50% among R-CHOP responders, with or without MR, there is a need for more effective treatment strategies in older DLBCL pts. No significant financial relationships to disclose.
Increased incidence of disease transformation and development of MDS/AML in Waldenstrom's macroglobulinemia (WM) patients treated with nucleoside analogues
Authors: Leleu X. P. , Manning R. , Soumerai J. , Hunter Z. R. , Moreau A. , Hatjiharissi E. , Roccaro A. , Adamia S. , Patterson C. J. , Ghobrial I. M. , Treon S. P. 
Published: March 2020

8018 Background: WM is an indolent B-cell lymphoma. NA are widely used in the treatment of WM, and are considered as appropriate first line agents for the treatment of WM (Gertz et al, Semin Oncol 2003; Treon et al, Blood 2006). Increased incidences of disease transformation and development of MDS/AML have been observed among patients with indolent B-cell malignancies receiving NA. We therefore sought to delineate the incidence for these events in a large population of WM patients treated at our institution. Methods: 326 previously treated patients with the consensus panel definition of WM, who received treatment with (n=173) or without (n=153) a NA were included in this analysis. Baseline characteristics between NA and non-NA treated patients were not significantly different and were as follows: median age 59 years; male/female ratio 1.4; median B2M 2.9 mg/L; serum IgM 3,000 mg/dL; BM involvement 40%; Hct 34%; WBC 5,100/ul, and PLT count 243,000/ul. For patients receiving NA, treatment consisted of either fludarabine (n=117; 68%), cladribine (n=48; 27%) or both (n=8; 5%). For non-NA treated patients, therapy included chlorambucil, rituximab, CVP, CHOP, thalidomide, and cyclophosphamide alone or in combination with rituximab, and alemtuzumab. Median follow-up of patients was 64 (range 10–270) months. Results: Among NA treated patients, 10 (5.7%) patients had transformation to an aggressive NHL (to DLBCL) (n=7; 4%) or developed MDS/AML (n=3; 1.7%). Disease transformation and development of MDS/AML occurred at a median time of 48 (range 7–114), and 48 (range 38–52) months following NA treatment, respectively. In contrast, among non-NA treated patients, only 1 patient demonstrated disease transformation (to DLBCL) at 10 months and no patients developed AML/MDS (p=0.025). Conclusions: These data demonstrate an increased incidence of disease transformation and development of MDS/AML among WM patients treated with NA. No significant financial relationships to disclose.
Confirmation of the prognostic value of the EORTC/WHO classification of primary cutaneous B-cell lymphoma in the United States: The Stanford University experience
Authors: Reddy S. A. , Kim Y. H. , Advani R. H. , Hoppe R. T. 
Published: March 2020

8028 Background: Primary cutaneous B cell lymphoma (CBCL) represent distinct clinicopathologic entities with superior prognosis compared to their nodal counterparts. In the new WHO/EORTC Classification of Cutaneous Lymphomas (WHOc), CBCL are classified as either Marginal Zone (MZ), Follicle center lymphoma (FC) or diffuse large cell-leg type (DLBCL leg-type). WHOc combined previous FL and DLBCL into the category of FC. Only DLBCL leg-type was considered to be aggressive and thus separately categorized. In order to confirm the utility of the WHOc categories, we reclassified our cases. Methods: Records of 154 CBCL patients (pts) managed at Stanford University were reviewed. A diagnosis of CBCL was made based on H&E evaluation, immunohistochemistry including CD20 staining, along with a negative systemic staging evaluation. All pts were reclassified according to the WHO/EORTC classification of CBCL. Overall Survival (OS), disease specific survival (DSS) and freedom from progression (FFP) were analyzed according to the method of Kaplan and Meier. Prognostic factors were evaluated by multivariate regression model and included initial therapy, histology, LDH, stage, IPI, extent of disease and anatomic location. Results: 154 cases were reclassified as follows: 87 FC, 58 MZ, and 9 DLBCL leg-type. The median follow-up was 46 months. The 5 year OS and DSS were 86 and 95% respectively. For the MZ and FC subtypes the % 10 year OS/DSS was: 93/100, and 86/97 respectively. For DLBCL leg-type the % 5 year OS/DSS was 17/33 respectively. There were 22 deaths, seven of which were disease specific (4 DLBCL-leg type and 3 were FC). FFP was unaffected by the type of therapy given (chemotherapy or skin-directed). Conclusions: Our series is the largest single center experience in CBCL. We confirm the utility of the WHOc in distinguishing categories with differing prognosis. The indolent histologies have an excellent outcome and can be managed with local skin-directed therapy. The outcome of pt with DLBCL leg-type is significantly worse than the FC or MZ types and warrants a more aggressive approach in management. No significant financial relationships to disclose.
Treatment and biology of lymphomatoid granulomatosis
Authors: Healey Bird B. R. , Grant N. , Dunleavy K. , Janik J. , Cohen J. , Pittaluga S. , Steinberg S. , Jaffe E. , Wilson W. 
Published: March 2020

8029 Background: LYG is a rare angiocentric-destructive process with EBV+ B-cells and reactive T-cells. LYG is graded with grades I-II showing rare-moderate large EBV+ B-cells (usually polyclonal or oligoclonal) and grade III showing numerous large EBV+ B-cells (usually monoclonal), likely reflecting progressive transformation. Historically, steroids and/or chemotherapy have a 14 mos median survival. Methods: We are investigating Interferon-a (I-a) for grade I/II and dose-adjusted EPOCH ±Rituximab (R) for grade III LYG. Results: Characteristics of 53 pts are: male sex 68%; median age (range) 46 (17–67) and median ECOG P.S. 1 (0–3). Disease sites include lung 98%, CNS 38%, kidney 15%, skin 17%, liver 19% and nodes 4%. On study LYG grades are I-30%, II-26% and III-44%. Prior treatment was none-28%, chemotherapy± R-34%, and steroids alone-40% of pts. For grades I/II, I-a is begun at 7.5 million IUs TIW and escalated as tolerated until disease regression and continued 1 yr after CR. Of 31 patients treated with I-a, PFS is 62% at the median f/u of 5.3 yrs. Of 25 evaluable pts (3 NE; 3 TE), 60% had sustained CR for a median of 60 mos (4–175). In 9 pts who progressed on I-a, grade III was found in 5. Thus, in 20 pts with only grade I/II, 75% had sustained CR with I-a. In 11 evaluable pts with CNS disease, 81% achieved remission with I-a alone. The median time to remission is 9 mos (3–40) and median I-a dose is 20 MIU (7–40). Among 24 pts receiving DA-EPOCH±R, PFS is 40% at the median f/u of 28 mos. Of 21 evaluable pts (2 NE, 1 TE), 66% achieved CR. OS of all 53 pts is 68% at the median f/u of 4 yrs. Median EBV viral loads in 29 pts at study entry were 18 copies/10e6 genome equivalents (0–22727) (normal<200). Lymphocyte subsets in 30 pts showed a median CD4–428 (24–2322) and CD8–165 cells/mm3 (42–1316). In 12 pts in CR and with serial values, the mean CD8 cells (131 ± 44) (p2= 0.013) but not CD4 cells (65 ± 75) increased with treatment. Conclusions: High dose I-a produces sustained remissions in grade I/II LYG and is effective in CNS LYG. DA-EPOCH±R can produce durable CRs in grade III LYG. We hypothesize LYG emerges in a compromised immune milieu and undergoes progressive transformation if not effectively treated. Historical results suggest steroids may allow transformation by compromising immune function. No significant financial relationships to disclose.
Effect of addition of rituximab to CHOP on survival of patients in both the GCB and non-GCB subgroups of diffuse large B-cell lymphoma
Authors: Fu K. , Perry K. D. , Smith L. M. , Hans C. P. , Greiner T. C. , Chan W. C. , Weisenburger D. D. , Bierman P. J. , Bociek R. G. , Armitage J. O. , Vose J. M. 
Published: March 2020

8040 Background: Diffuse large B-cell lymphoma (DLBCL) includes at least two prognostically important subgroups, i.e. germinal center B-cell (GCB) and activated B-cell (ABC) DLBCL, which were initially characterized by gene expression profiling and subsequently validated by immunostaining. Bcl-2 has also been identified as a prognostic indicator in the ABC subgroup. However, with the addition of rituximab (R) to standard chemotherapy, the prognostic significance of this subclassification of DLBCL is unclear. Methods: We studied 119 cases of de novo DLBCL including 70 cases treated with R-CHOP and 49 cases treated with CHOP. The cases were assigned to either the GCB or non-GCB subgroups using the methodology described by Hans et al (Blood 2004; 103:275). Characteristics of the patients were compared using the Chi-square test. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan Meier method and compared with the log-rank test. Results: The median age of the 119 patients was 67 years, ranging from 20 to 90 years, and there were 62 males and 57 females. The clinical characteristics of patients treated with CHOP versus R-CHOP, including the IPI, were comparable. R-CHOP was more effective than CHOP with improved 5-year EFS (63% vs 41%, p=0.013) and OS (78% vs 47%, p<0.001). In both patient groups treated with R-CHOP or CHOP, the GCB subgroup had a significantly better 5-year EFS and OS compared to the non-GCB subgroup (OS: 91% vs 64% for R-CHOP, p=0.0073; 67% vs 31% for CHOP, p=0.034, respectively). Additionally, both the GCB and non-GCB subgroups treated with R-CHOP had a significantly improved OS compared to their respective subgroups receiving CHOP alone (GCB, p=0.015; non-GCB, p=0.019). Bcl-2 expression was not a significant predictor in either the GCB or non-GCB subgroups treated with R-CHOP (OS, GCB: p=0.32; non-GCB: p=0.43). Conclusions: In this retrospective study, we demonstrate that subclassification based on the cell of origin continues to have prognostic significance in patients with DLBCL treated with R-CHOP. Addition of rituximab to CHOP improves the overall survival of patients with DLBCL in both the GCB and non-GCB subgroups. No significant financial relationships to disclose.
High-dose melphalan (MEL) based autotransplants (AT) for multiple myeloma (MM): The Arkansas experience since 1989 in more than 2,800 patients
Authors: Pineda-Roman M. , Haessler J. , Hollmig K. , Anaissie E. , van Rhee F. , Zangari M. , Tricot G. , Mohiuddin A. , Crowley J. , Barlogie B. 
Published: March 2020

8043 Background: The dose-response effect for MEL has been safely exploited through the use of AT. Long-term follow-up studies from large centers are critical to understand who benefits most and who should be considered for alternative treatment approaches. Methods: 2,836 patients receiving at least one MEL AT were considered. Kaplan-Meier analysis was used to estimate median event-free survival (EFS) and overall survival (OS). Cox regression was used to evaluate independent prognostic factors of EFS and OS from AT. Results: Of the 2,836 patients, 979 were enrolled into front-line Total Therapy protocols 1/2/3 (TT); 1,064 were entered on protocols for previously treated patients (non-TT); and 793 were treated off protocol (non-P). Overall median EFS and OS from 1st AT are 31mo and 53 mo; 10-yr EFS and OS were 19% and 24%; 15% survived >15 yr. The 5 strongest favorable OS features included TT (HR 0.46, p<0.001), absence of cytogenetic abnormalities (no CA) (HR 0.48, p<0.001), B2M <3 mg/L (HR 0.46, p<0.001), albumin >=3g/dL (HR 0.45, p<0.001) and platelet count >=100.000/microL (HR 0.41, p<.001), so that 10-yr OS rates were 58% with 5, 24% with 4, 16% with 3, 4% with 2 and 0% with =<1 favorable parameter (p<0.0001). The corresponding median durations of EFS were 80 mo, 37 mo, 27 mo, 18 mo and 7 mo (p<0.0001). Conclusion: This large single institution experience demonstrates that > 10 yr OS can be accomplished in over one-half of the 16% of all patients presenting without CA, with low levels of B2M and albumin, high platelet count and receiving TT. The worst constellation affected 3% of all patients presenting with at most 1 good-risk feature whose 5-yr survival was only 7%. These data should serve as guidepost for MM investigators and patients alike, against which newer treatments should be measured. No significant financial relationships to disclose.
Predictors of initial treatment in older adults with follicular non-Hodgkin lymphoma
Authors: Elkin E. B. , Portlock C. , Yahalom J. 
Published: March 2020

8054 Background: Multiple treatment options are available for patients with follicular lymphoma (FL), including expectant management (EM), radiation therapy (RT), various chemotherapy (CTX) regimens, and immunotherapy (IM). Older age is a well established adverse prognostic factor in FL. Our objective was to identify factors associated with initial treatment in a population-based cohort of older adults with FL. Methods: Using SEER cancer registry data linked with Medicare claims, we identified cases of FL diagnosed in adults age 66 and older from 1995–2002. Initial treatment was defined as EM, CTX alone, RT alone, or combined CTX and RT based on Medicare claims within six months of diagnosis. IM with rituximab was grouped with CTX. We assessed the effects of demographic and clinical characteristics on the odds of receiving each treatment. In patients who initially received EM, we estimated the time until first treatment. Results: In 3,241 FL patients, the most common initial treatment strategy was CTX alone (n=1,351, 42%), followed by EM (n=1,242, 38%), RT alone (n=434, 13%) and combined CTX+RT (n=214, 7%). Treatment varied widely by age ( Table ). In multivariable analysis, predictors of EM included older age at diagnosis (p<0.0001), greater comorbidity (p<0.001) and earlier stage of disease (p<0.01). Use of CTX and RT, each alone or in combination, decreased with increasing age (p<0.0001 for any CTX, p<0.05 for any RT). Later disease stage was positively associated with CTX (p<0.0001) and negatively associated with RT (p<0.0001). Over time, use of CTX increased (p<0.05) and use of RT decreased (p<0.05). About 70% of EM patients remained treatment-free at two years, and the median time until first treatment for this group was 50 months. Conclusions: A substantial fraction of FL patients over age 65 do not receive any cancer-specific treatment at diagnosis, and most of those patients will remain untreated for more than four years. The potential benefits of earlier or more aggressive treatment of these patients remain to be demonstrated. [Table: see text] [Table: see text]
MicroRNA regulation in mantle cell lymphoma
Authors: Chen R. , Patel S. , Bemis L. , Robinson W. , Myint H. 
Published: March 2020

8056 Mantle Cell Lymphoma (MCL) represents only 5–10% of all non-Hodgkins lymphomas, making it an uncommon but difficult form of lymphoma to treat. It has the worst prognosis among the B cell lymphomas with median survival of three years. The genetic hallmark of MCL is a t(11;14) q32 translocation which results in ectopic and dysregulated expression of cyclin D1. Recent comparative genomic hybridization studies have identied Syk as another gene important in the pathogenesis of MCL. Previous studies have suggested that post transcriptional regulation of Cyclin D1 and Syk may be important the pathogenesis of in MCL. MicroRNAs are a new class of abundant small RNAs that play important regulatory roles at the post transcriptional level by binding to the 3’ untranslated region (UTR) of mRNAs blocking either their translation or initiating their degradation. There have been numerous reports of misregulation of microRNAs and their targets in human cancers. We hypothesized that altered microRNA regulation of cyclin D1 and/or Syk may be present in MCL. Based on bioinformatics, we identified 8 microRNAs and their putative docking sites in either Cyclin D1 and Syk. We then examined their integrity in MCL cell lines, and identified a mutation in the 3’UTR of Syk at the docking site of 1 mir-452* and a SNP in mir-458. Using a GFP reporter construct with the mutated Syk 3’UTR we demonstrated that this mutation resulted in altered microRNA function. We also show that mimics of the microRNA leads to down regulation of Syk protein. This data suggests that microRNA regulation of important genes in MCL may be compromised and play a role in the development and progression of this disease. No significant financial relationships to disclose.