bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of radiologic diagnosis in peripheral clinical IA lung cancers—A prospective study for radiological diagnosis of peripheral early lung cancer (JCOG 0201)
Authors: Suzuki K. , Koike T. , Shibata T. , Kusumoto M. , Asamura H. , Nagai K. , Tada H. , Mitsudomi T. , Tsuboi M. , Kato H. 
Published: March 2020

7220 Background: The spread of computed tomography (CT) screening for lung cancer (LC) leads to the increased detection of small sized LC. Performance and accuracy of radiological diagnosis had not been evaluated and indication of limited surgery for CT detected LC remains unknown. Methods: Between Dec/2002 and May/2004, a prospective study was performed. Patients (pts) having peripheral lung adenocarcinoma (AD) of T1N0M0 were eligible. Radiologic findings of LC were evaluated as to ground-glass opacity (GGO) with thin-section CT (TSCT). A radiological non-invasive cancer (NIC) was defined as a tumor having consolidation less than half of the maximum tumor dimension. A pathological NIC, which is future candidate for limited surgery, was defined as a tumor with no lymph node mets, lymphatic, nor vascular invasion. A validity of radiological diagnosis by above criteria was investigated. Primary endpoint is specificity as the proportion of pts with radiologically diagnosed invasive LC in pts with pathologically diagnosed invasive LC. Planned sample size was 450 with precision-base. We expected that lower limit of 95% CI of specificity is over 97%. Results: Totally 811 pts were enrolled onto the study at 31 institutions, including 357 men. Age ranged 27 to 75 (median 61). Primary endpoint was evaluated on central-reviewed 545 AD resected by lobectomy. Specificity and sensitivity for the diagnosis of pathological NIC were 96.4% (161/167 95% CI 92.3% to 98.7%) and 30.4% (115/378 95% CI 25.8% to 35.3%), respectively. As to relationship between radiologic NIC and pathological nodal involvement, specificity and sensitivity for the diagnosis were 98.3% (59/60 95% CI 91.1% to 100%) and 24.7% (120/485 95% CI 21.0% to 28.8%), respectively. Conclusions: Our pre-determined criterion for the specificity was not confirmed, and candidates for limited surgical resection can not be selected based on our criteria. However, radiological diagnosis of node-negative LC with TSCT was well coincide, and the criterion might be used for selecting node negative peripheral LC. A phase II study of limited surgical resection for peripheral LC 2.0 cm or less in size is now planned based on the results of exploratory analysis of this study. No significant financial relationships to disclose.
Prognostic value of clinicopathological factors in operated stage I non-small cell lung cancer (NSCLC)
Authors: Nakahara R. , Suzuki H. , Matsuguma H. , Igarashi S. , Miyazawa N. 
Published: March 2020

7222 Background: Recently adjuvant chemotherapy has improved survival in resected stage I, especially stage IB NSCLC. While some cases with stage IA NSCLC have poor prognosis, there are no reliable clinicopathological markers to predict cancer related death. This study was conducted to identify the prognostic factors for resected stage IA and IB patients. Methods: We retrospectively analyzed 318 cases that were diagnosed with pathological stage I NSCLC from 1986 to 2000 at Tochigi Cancer Center. Various clinical and pathologic factors were reviewed, and the risk of a cancer related death was investigated. Analyzed factors were as follows: sex, age, smoking status, preoperative serum CEA level, tumor histological type, pathological differentiation, tumor size, lymphatic invasion (ly), vascular invasion (v), and pleural invasion (p). Results: The cancer specific 5-year survival rate for each stage were estimated to be 91% foe stage IA (n = 198) and 66% for stage IB (n = 120). In the stage IA subset, the univariate analysis revealed the following five factors to be poor prognostic factors: age 65 < (p = 0.008, Risk Ratio = 1.76), high CEA level (p < 0.001, RR = 2.09), tumor size 2 cm < (p = 0.008, RR = 1.75), ly (+) (p = 0.007, RR = 1.87), and v (+) (p = 0.003, RR = 1.77). The 5-year survival rate for stage IA patients that have three or more factors was 67% (n = 43). In the stage IB subset, the univariate analysis of clinicopathological factors revealed tumor size 4 cm < (p = 0.004, RR = 1.53), v (+) (p = 0.02, RR = 1.45), and no pleural invasion (p0) (p = 0.004, RR = 0.64) to be prognostic factors. The 5-year survival rate for stage IB patients that have all the good prognostic factors (tumor size 4 cm ≥, v(-), and p0) was 96% (n = 26). Conclusion: Our analysis suggests that the combination of prognostic factors revealed the poor prognostic group equal to stage IB patients in stage IA group. On the other hand, combination of prognostic factors revealed the good prognostic group in stage IB patients. It should be considered to do adjuvant chemotherapy with poor prognostic stage IA patients and avoid with good prognostic stage IB patients. No significant financial relationships to disclose.
Biomarker correlates of survival in NSCLC: Role of RXRβ and PPARγ in mediating bexarotene impact on patient survival
Authors: Negro-Vilar A. , Gatzemeier U. , Ramlau R. , Sun S. L. , Negro-Vilar R. , Hermann T. , Zhang J. K. , Dziewanowska Z. 
Published: March 2020

7227 Background: Bexarotene is a selective modulator of retinoid X nuclear receptors (RXRs), which form heterodimers with many other nuclear receptors playing a critical role in cell growth, differentiation, and apoptosis. Loss of RXRs is seen in many advanced tumors, including NSCLC and higher RXR levels in NSCLC lung biopsies (stages I-III) have been correlated with longer overall survival. Two large first line NSCLC Phase III trials reported at ASCO 2005 (SPIRIT I and II) showed that while no benefit in overall survival was seen adding bexarotene to two chemo regimens, a large (36%) subpopulation of patients in both trials that had high grade hypertriglyceridemia in response to bexarotene had significantly longer survival. A retrospective analysis was conducted to evaluate the baseline characteristics of these patients and to examine the level of expression of RXR and one of its partners (PPARγ) in lung tumor tissue biopsies obtained from a subgroup of patients in both studies. Methods: RXRs (α,β,γ) and PPARγ expression levels in lung tumor tissue from patients in SPIRIT I and II trials (stage IIIB/IV) taken prior to study entry were assessed by Q-PCR analysis of RNA isolated from microdissected lung tumor tissue biopsies. Cox regression and Kaplan-Meier survival estimation were used for statistical evaluations. Results: In an initial subset of 41 patients, RXRβ expression in lung tumor showed positive correlation with survival. High RXRβ = longer survival (median survival 438 days), low RXR shorter (MS = 317). Treatment with bexarotene increased the differences (RXRβ Hi, MS = 627 days; RXRβ low = 211 days). PPARγ showed a negative correlation with survival and those patients with RXRβ Hi/PPARγ low ratios had the longest MS (627 days vs. 226 days for the RXRβ low/PPARγ high group), a difference that was magnified by bexarotene treatment. Conclusions: RXRβ expression level correlates with a positive survival in late stage NSCLC while PPARγ shows negative correlation. Bexarotene treatment enhances the survival differences, supporting an involvement of triglyceride and lipid metabolism as regulated by these two key nuclear receptors in the longer survival seen in the 215 patients in the high triglyceride subgroup. [Table: see text]
A computer program designed to assist in NSCLC adjuvant therapy decision making
Authors: Ravdin P. M. , Davis G. J. 
Published: March 2020

7230 Background: The goal the computer program, Adjuvant! for NSCLC, is provide the health professional, and the NSCLC patient with information that might be helpful when deciding about adjuvant chemotherapy for completely resected Stage 1 to Stage 3A disease. The 4 elements of this decision are: estimates of prognosis, estimates of the efficacy of adjuvant chemotherapy, estimates of completing mortality, and estimates of toxicity. Methods: Estimates of prognosis are based on an analysis of 17, 130 patients in the SEER registry. Estimates for 5 year disease specific mortality for Stage 1A, 1B, 2A, 2B, and 3A disease are 22%, 37%, 51%, 63%, and 70%. Multivariate analysis justifies using tumor size, histologic grade, and BAC histology for refinement of prognostic estimates for Stage 1 patients. A small subgroup of Stage 1 patients (with tumors < 10mm, low grade, BAC histology) could be identified with a 5 year disease specific mortality risk of <10%. Estimates of the efficacy of chemotherapy were derived from meta-analyses. A proportional risk reduction of 20% is used by the program as the default efficacy estimate for platinum-based therapy. Pop-ups and help files discuss areas of uncertainty and controversy. The user has the option to adjust the default efficacy estimate to the more optimistic efficacy estimates of some of the recent trials, or to take into account some of the uncertainty as to whether adjuvant chemotherapy works as well in Stage 1 disease. SEER data shows the average NSCLC patient has competing mortality rates higher than would be suggested by chronologic age. Regimen specific risks of treatment related toxicity is given by the program. In the over 100 pages of help files there is a detailed discussion of the clinical evidence, adjuvant therapy guidelines, ongoing clinical trials, and corollary areas (radiotherapy, neoadjuvant therapy, biomarkers, etc.) Results: The program projects that for patients with favorable Stage 1 tumors the absolute OS benefit of therapy may be as low as 1% (of the same size as the risk of treatment related mortality), but for patients with Stage 2 and 3A disease the 5 yr OS benefit may be ∼10%. Conclusions: The impact of this tool on physician and patient knowledge about the adjuvant therapy of NSCLC will be presented. [Table: see text]
The impact of initial treatment of advanced stage indolent lymphoma on the risk of transformation
Authors: Al-Tourah A. J. , Gill K. K. , Hoskins P. J. , Klasa R. J. , Savage K. J. , Sehn L. H. , Shenkier T. N. , Gascoyne R. D. , Voss N. J. , Connors J. M. 
Published: March 2020

7510 Background: The impact of initial treatment of indolent non-Hodgkin’s lymphoma (NHL) on the risk of transformation (TR) to aggressive NHL is unknown. High LDH and advanced stage at diagnosis have been shown to be predictive for TR; however, the effect of initial treatment is difficult to estimate as most series included heterogenous patient (pts) populations. Methods: As part of a large retrospective analysis examining TR (n = 698), we identified pts from 2 consecutive phase II studies conducted at the British Columbia Cancer Agency. Both studies had identical inclusion criteria: diagnosis of indolent NHL, no prior treatment, age16–60 y and advanced stage disease (III/ IV or I/ II with B symptoms or bulky disease ≥10cm). The first study included use of BPVACOP (bleomycin, cisplatin, etoposide, doxorubicin, cyclophosphamide,vincristine and prednisone, followed by involved field irradiation (RT) to original nodal sites of lymphoma. The second used combination alkylator-purine analogue (cyclophosphamide- cladrabine or fludaribine and prednisone). The definition of TR was based on either histological confirmation (HIST) or clinical features (CLIN), defined as one or more of the following: rapid discordant nodal or extranodal growth; sudden rise in LDH to > 2 x previous baseline; involvement of unusual extranodal sites; or hypercalcemia. Results: 260 pts were identified. BPVACOP+RT (n = 140), alkylator-purine analogue (n = 120). Median age 46 y (19–60). Follicular histology in 133 (94%) and 105 (87%), respectively. The majority were stage III/IV (89%) with equal proportions in each cohort. With a median follow-up (FU) for living pts of 90 months (1–225), 26 (18%) pts treated with BPVACOP+RT developed TR, 16 of which were confirmed with biopsy, versus 32 (27%) in the alkylator-purine group, of which 18 had biopsy confirmation. The 5 y risk of TR for BPVACOP+RT was 9% compared to 24% for the alkylator-purine analogue group (p < 0.0095). The annual risk of TR through 10 y of FU was 1.5% and 3.0%, respectively. The post-TR 5 y OS of all 58 pts with TR was 19%. Pts with TR based on CLIN vs HIST criteria did not differ in their outcome. Conclusions: The use of an anthracycline-based regimen as initial treatment for advanced stage indolent NHL is associated with a marked reduction in the risk of future TR. No significant financial relationships to disclose.
Long-term follow-up of high-dose treatment (HDT) with autologous haematopoietic progenitor cell support in 702 patients (pts.) with follicular lymphoma (FL). An EBMT registry study
Authors: Montoto S. , Rohatiner A. Z. , Canals C. , Gisselbrecht C. , Fouillard L. , Milpied N. , Haioun C. , Taghipour G. , Schmitz N. , Goldstone A. H. 
Published: March 2020

7526 Background: HDT with stem cell rescue has been increasingly used in pts. with FL. The aim of this retrospective analysis was to evaluate the outcome of a large series of pts. who received HDT for FL. Patients: From 1979 to 1995, 702 pts. (median age: 45, range: 17–68 yrs.) underwent HDT with a TBI-containing regimen in 407 cases and chemotherapy-based regimens in 276 (BEAM, 164). The median time from diagnosis to HDT was 2.2 yrs. Disease status at the time of HDT was as follows: CR, 323 pts. (1st: 138; 2nd: 141; 3rd: 44); PR, 170 pts.; recurrence/progression, 187 pts. (“sensitive”, 152; resistant, 20; untested, 15); primary refractory, 22 pts. The source of progenitor cells was bone marrow (BM) in 384 pts. (55%), peripheral blood progenitor cells (PBPC) in 288 (41%) and BM + PBPC in 30 (4%). Results: 353/702 pts. (50%) developed recurrent lymphoma at a median of 1.7 yrs. (range: 0.2 to 13.3) after HDT. 5-year PFS after HDT was 43%. On multivariate analysis, age at HDT <45 yrs. and HDT in CR1 correlated with longer PFS; refractory disease was the only variable predictive for risk of recurrence. 23 pts. developed secondary MDS/AML, in 18 cases after receiving TBI. With a median follow-up of 10.2 yrs., 338 patients have died, 96 without lymphoma progression. The 5-year non-relapse mortality (NRM) was 9%. On multivariate analysis, age > 45 at HDT, refractory disease at HDT and TBI were associated with a higher NRM. 5-yr and 10-yr OS from HDT were 64% and 52%, respectively. For pts. treated with HDT in CR1, 10-yr OS and PFS from HDT were 71% and 46%, respectively. The variables that predicted for a longer OS in the multivariate analysis were younger age at HDT, CR1 at HDT and the use of a non TBI-containing regimen. The effect of TBI on NRM and OS was mostly as a consequence of late mortality. Conclusions: This analysis confirms that the best outcome was associated with younger age and treatment in CR1. In addition, in this study TBI was associated with a negative impact on survival. No significant financial relationships to disclose.
Phase I/II trial of Arginine Butyrate and ganciclovir in Epstein-Barr virus-associated lymphoid malignancies
Authors: Faller D. V. , Hermine O. , Small T. , Suarez F. , O’Reilly R. , Boulad F. , Fingeroth J. , Mentzer S. J. , Klein C. , Horwitz S. , Perrine S. P. 
Published: March 2020

7542 Background: Malignancies associated with latent Epstein-Barr virus (EBV) are resistant to nucleoside-type anti-viral agents because the viral enzyme target of these drugs, thymidine kinase (TK), is not expressed. Short-chain fatty acids, such as butyrate, induce EBV-TK expression in latently-infected B cells. In preclinical studies, we have shown that butyrate sensitizes EBV(+) lymphoblastoid cells, tumor lines and primary lymphoma cultures to apoptosis induced by ganciclovir. Methods: We conducted a Phase I/II trial of Arginine Butyrate in combination with ganciclovir in patients with refractory EBV(+) lymphoid malignancies to evaluate toxicity, pharmacokinetic parameters, and clinical responses. Fifteen patients with heavily-pretreated, refractory EBV(+) lymphoid malignancies, consisting of monoclonal refractory lymphoproliferative disease (PTLD), B cell non-Hodgkin’s lymphomas (NHL) (including one HIV-associated anaplastic B cell lymphoma), T cell NHL (including one cutaneous lymphoma), T/NK cell lymphomas, and Hodgkin disease were studied. Ganciclovir was administered twice daily and Arginine Butyrate was administered in an intra-patient dose-escalation. Arginine Butyrate was instituted at 500 mg/kg/day by continuous infusion, and escalated to 2000 mg/kg/day, as tolerated. Results: The MTD for Arginine Butyrate was established as 1000 mg/kg/day. Overall the combination was well-tolerated, with the most common toxicities being nausea and headache. Complications from rapid tumor lysis occurred in three patients, including acute hepatic necrosis in one patient. Reversible grade 3–4 somnolence or stupor occurred in three patients at Arginine Butyrate doses of greater than 1000 mg/kg/day. Ten of fifteen patients showed significant anti-tumor responses, with 5 CR and 5 PR. In certain patients who demonstrated a clinical CR, subsequent pathological analysis showed elimination of all tumor cells. Conclusions: The combination of Arginine Butyrate and ganciclovir was reasonably well-tolerated and appears to have significant biological activity in vitro and in vivo against refractory EBV(+) lymphoid malignancies. No significant financial relationships to disclose.
Defining Burkitt’s lymphoma (BL) with cytogenetics: LY10, a prospective clinicopathological study of dose-reduced (dr) CODOX-M/IVAC in patients with 100% Ki-67 staining B-cell non-Hodgkin’s lymphoma (NHL)
Authors: Walewski J. , Mead G. , Jack A. , Barrans S. , Radford J. , Clawson S. , Stenning S. , Qian W. 
Published: March 2020

7557 Background: Previous studies suggest that CODOX-M/IVAC is effective therapy for BL (Ann Onc 2002 13:1264–74), however the diagnosis of BL in this and other studies was not based on modern immunochemistry and cytogenetics and is unreliable. To re-evaluate this question we prospectively studied a population of patients (pts) with aggressive B-cell lymphoma (100% Ki-67+) uniformly treated with dr CODOX-M/IVAC. Methods: Pts ≤65 years with B-cell lymphomas showing 100% Ki-67, considered fit for chemotherapy, received either dr CODOX-M x 3 or dr CODOX-M/IVAC x 4 according to a modified international prognostic index (IPI). Chemotherapy was modified by methotrexate dose reduction to 3g/m2. Pts >65 years had further dose reductions; unfit pts were studied pathologically only. Tumours were characterised using both an extended panel of antibodies and interphase FISH on paraffin sections for the presence of the C-MYC and BCL-2 rearrangements. Results: Of 126 pts reviewed centrally, 5 were ineligible; 53 were diagnosed as BL, each based on the combination of the presence of re-arrangement of C-MYC as a sole abnormality, germinal centre phenotype and p53 abnormality. The final 68 cases were highly heterogenous with respect to tumour phenotype and cytogenetics and were diagnosed as diffuse large B-cell lymphoma (DLBCL). Median age (all pts) was 44 years (range 17–83), with 23 aged >65. Compared with the DLBCL pts, BL pts were significantly younger (mean 38yrs vs 53 yrs, p < 0.001), had more marrow involvement (45% vs 24%, p = 0.02) and male predominance (83% vs 65%, p = 0.03). Of 104 pts entered into the clincal study, 32 pts (10 BL, 22 DLBCL, IPI 0,1) received dr CODOX-M x 3 and 72 (39 BL, 33 DLBCL, IPI >1) received dr CODOX-M/IVAC x 4. With median follow-up of 15 months (range 1 to 37), 1 year progression-free survival was 58%, 95% CI 48%-68% (54% BL vs 62% DLBCL) and 1 year survival 61% 95% CI 51%-71% (55% BL vs 66% DLBC). Conclusions: The study shows Ki67 is not an accurate approach to the diagnosis of BL and the use of immunocytochemistry and FISH is essential. BL and DLBCL as defined differ markedly clinically. Preliminary data suggest that dr CODOX-M/IVAC has similar activity in both histologies. No significant financial relationships to disclose.
Phase II study of preemptive high dose chemotherapy and autologous stem cell transplantation for lymphoma based on early FDG-PET scanning
Authors: Kasamon Y. L. , Wahl R. , Ziessman H. , Garrett-Mayer E. , Jones R. J. , Ambinder R. F. , Flinn I. W. , Swinnen L. J. 
Published: March 2020

7561 Background: [18F] FDG-PET after only 2–4 cycles of initial chemotherapy is highly prognostic in patients (pts) with aggressive lymphoma, with reported relapse rates of 71–100% if PET demonstrates residual viable disease. We hypothesized that midtreatment PET could optimize pt selection for preemptive transplantation through early risk stratification. Methods: A phase II, single center trial was activated in 2/2004. Pts with newly diagnosed aggressive non-Hodgkin’s lymphoma underwent PET-CT on days 11–20 of cycle 2 or 3 of (R)CHOP. Regardless of IPI, pts whose PET was considered positive for macroscopic residual lymphoma received 2 cycles of (R)ESHAP or (R)ICE, followed by autologous transplantation (busulfan-cyclophosphamide conditioning). Pts with negative interim PET completed standard therapy. We aimed to transplant ≥20 pts to detect a ≥25% absolute improvement in 2-year event-free survival (EFS) to 45%, versus 20% in a historical cohort of PET positive pts who did not receive early transplantation (85% power and two-sided alpha of 0.05). An ongoing imaging analysis of gradations of FDG uptake, scored as 0 to 4+, will be correlated with outcome. Results: As of 1/6/2006, 41 evaluable pts have been accrued, 39 with large B-cell lymphoma (8 primary mediastinal), 1 follicular large cell, 1 peripheral T-cell. Median age at diagnosis was 50 (20–78); 26 pts were stage III or IV. Twenty-five pts (61%) had a positive midtreatment PET. Of 26 pts with IPI of 0–2, 17 (65%) had positive PET; of 13 pts with IPI of ≥3, 8 (62%) were positive; 2 pts had undetermined IPI. The actuarial 1-year EFS from the time of midtreatment imaging is 78% for the group as a whole, 69% for PET positive pts, 81% for PET negative pts. Twenty pts have completed transplant, and 2 were ineligible because of early disease progression. Two transplant recipients have relapsed. Treatment-related mortality has been limited to 1 death from veno-occlusive disease. Conversion from PET positive to negative at initial post-transplant assessment occurred in 68%. The actuarial 1-year EFS after transplantation at 10 month median follow-up is 82%. Conclusions: Immediate intensification of therapy for poor-risk pts identified by midtreatment PET has been feasible and so far very promising. [Table: see text]