bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-dose 3D chemoradiotherapy trials in stage III non-small cell lung cancer (NSCLC) at the University of North Carolina: Long-term follow up and late complications
Authors: Lee C. B. , Socinski M. A. , Lin L. , Moore D. T. , Morris D. E. , Halle J. S. , Rosenman J. G. 
Published: March 2020

7145 Background: Combined modality treatment is the standard of care for patients (pts.) with unresectable stage III NSCLC. Dose escalation of radiotherapy and the use of concurrent chemotherapy are two strategies attempting to improve survival and locoregional control. The intensification of therapy increases the risk of both early and late treatment related toxicities. Methods: From 5/1996 to 8/2004, 112 stage III NSCLC pts. were entered into 4 Phase I/II trials to assess the safety and feasibility of high-dose (74–90 Gy) thoracic conformal radiotherapy (TCRT) in QD or BID fractions. All pts. were treated with platinum-based induction chemotherapy; 3 of the trials also used concurrent chemotherapy. Results: The median follow up of survivors (29/112) on these trials was 4.9 years. The overall response rate after combined modality therapy was 47% (53/112) (CR 4%, 5/112; PR 43%, 48/112). 27% (30/112) had stable disease. The median survival (with 95% CI) was 24 months (18–31 months). 1-, 3-, and 5-year overall survival was 69% (60–77%), 36% (27–45%), and 24% (16–33%) respectively. Late complications of therapy (defined as >90 days post radiotherapy reported to date) are displayed in the table. Two pts. developed a second primary (1 lung, 1 liver carcinoid). In total, 22% (25/112) had late complications. These patients appear to have a significantly better overall survival (p = .007). 12% (13/112) had a brain-only recurrence, although this did not seem to significantly impact overall survival (p = .82). Conclusions: 1) High-dose TCRT is feasible and results in promising survival outcomes. 2) Late complications occur in a minority of patients suggesting the potential benefit of more aggressive TCRT is not outweighed by its risk. 3) Interestingly, brain-only recurrences did not significantly impact survival in these trials. [Table: see text] [Table: see text]
Evaluation of epidermal growth factor receptor (EGFR) mutations as predictive and prognostic indicators in patients with adenocarcinoma of the lung treated with conventional chemotherapy
Authors: Fukui T. , Ohe Y. , Takano T. , Tsuta K. , Nomoto K. , Furuta K. , Sekine I. , Kunitoh H. , Matsuno Y. , Tamura T. 
Published: March 2020

7165 Background: EGFR mutations are associated with the responses to EGFR-tyrosine kinase inhibitors (TKI) in patients (pts) with adenocarcinoma of the lung. The E746-A750 deletion and L858R substitution mutations are the most common, as previously described. However, their implications in pts treated with conventional chemotherapy are unclear. To evaluate the predictive and prognostic value of the EGFR mutations, we studied pts with adenocarcinoma of the lung treated with conventional chemotherapy. Methods: We reviewed pts with advanced or recurrent chemotherapy naïve adenocarcinoma of the lung who received systemic chemotherapy between January 1999 and July 2001. Deletion in exon 19 and missense mutation (L858R) in exon 21 from small biopsy or cytology samples were analyzed by a high-resolution DNA melting analysis technique. Results: A total of 101 pts, all Japanese, could be analyzed. Patient characteristics were as follows: median age: 62 (37–84) years; female/ male: 39/ 62; never/ former/ current smoker: 47/ 23/ 31; and platinum-based/ non-platinum regimen: 81/ 20 (18 pts received EGFR-TKI later). 43 pts (42.6%) had EGFR somatic mutations; deletion in 24 pts, and a point mutation (L858R) in 19 pts. PR/ SD/ PD/ NE was observed in 11/ 24/ 7/ 1 pts with EGFR mutations and in 13/ 28/ 15/ 2 pts without the mutations, respectively. The response rate was similar (26% vs. 22%, p = .71) in the two subgroups. The median survival duration of the pts with EGFR mutations was 14.9 months (n = 43, including the 11 pts treated with EGFR-TKI later), as compared with 11.0 months (n = 58, including the 7 pts treated with EGFR-TKI later) in the pts without EGFR mutations (p = .09). Another analysis which handle the start of gefitinib administration as a censoring showed similar results (p = .24). Conclusions: EGFR mutations were not good predictors of tumor response to conventional chemotherapy. The overall survival tended to be longer in the pts with EGFR mutations, but prognostic value of these mutations for survival in pts with advanced adenocarcinoma of the lung was not statistically significant. No significant financial relationships to disclose.
Gastrointestinal hemorrhage in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib and celecoxib
Authors: Fidler M. J. , Argiris A. , Patel J. D. , Johnson D. H. , Sandler A. , Villaflor V. , Coon J. , Buckingham L. , Bonomi P. 
Published: March 2020

7172 Background: Erlotinib (E) was associated with superior survival in a phase III trial of previously treated advanced NSCLC patients (pts). Celecoxib (C) has been shown to potentiate the apoptotic and growth inhibitory effects of E in pre-clinical models. Methods: This was a phase II trial of E plus C in advanced NSCLC pts that failed one prior chemotherapy regimen. Primary endpoint: efficacy; secondary endpoint: toxicity. Pts received C (400mg b.i.d.) and E (150mg daily) until disease progression. Planned accrual: 40 pts. Results: 26 pts with stage IIIB/IV NSCLC were enrolled. Patient (pt) characteristics: male 65%; median age 66; ECOG performance status 0/1- 96%. Eighteen pts had tissue available for FISH and EGFR mutation analysis: 50% had chromosome 7 polysomy (> 4 copies per cell); none had EGFR gains (>2 EGFR/chromosome 7). Two pts had an EGFR gene mutation (1 exon 19, 1 exon 21). Response results: partial response- 2 pts (1 with exon 19 mutation), stable disease- 8 pts, and progressive disease- 16 pts (1 with exon 21 mutation). Median progression free survival (PFS) and overall survival (OS): 1.9 and 10.2 months, respectively. Grade 3/4 upper gastrointestinal bleeding (GIB) occurred in 4 pts prompting study closure. One pt was on therapeutic dalteparin and two pts receiving warfarin developed marked INR prolongation (INR >10). The fourth pt had a history of peptic ulcer disease. Platelet counts at time of GIB: 142 - 559. Three pts had endoscopy and gastric or duodenal ulcers were found in all three cases. No pts were taking anti-acid medication at the time of GIB. No other pts were on therapeutic anticoagulation. Three pts without upper GIB were taking low-dose aspirin. Other toxicities: 85% grade 1/2 rash; 65% grade 1/2 diarrhea, 30% grade 1/2 nausea, 30% grade 1/2 fatigue (one grade 3 fatigue); one grade 3 pneumonitis, one grade 3 esophageal stricture. Conclusions: These observations suggest that C plus E may be associated with increased incidence of gastrointestinal ulceration and GIB and that the regimen should not be given to pts with a previous history of peptic ulcer disease or to pts requiring therapeutic anticoagulation. Based on response rate, PFS, and OS in this group of pts, it appears that results with E and C are similar to those reported for E alone. [Table: see text]
Cohort KBP-2000-CPHG: Evaluation of prognosis factors for survival in primary bronchial cancer (PBC)
Authors: Blanchon F. , Grivaux M. , Zureik M. , Asselain B. , Breton J. , Duvert B. , Legroumellec A. , Level M. , Berthiot G. , Carlier M. 
Published: March 2020

7204 Background: PBC has a guarded prognosis despite advances in treatment. The main epidemiologic changes observed during the last fifteen years are the strong progression in its incidence in women and the increase in adenocarcinomas. A prospective study of overall survival and survival according to sex and prognosis factors was set up from the cohort of study KBP-2000-CPHG. Methods: KBP-2000-CPHG is a prospective epidemiological study conducted throughout the year 2000 on histologically confirmed PBC patients treated in general hospitals. 5,667 patients were included. A survival study based on patient outcomes was launched between September 2004 and March 2005 in 137 centres. Each centre had to provide information on the vital status of its patients with, in the event of death, the date and cause. In the absence of vital status data, a graduated tracing strategy was set up including the interrogation of various files: city hall of the place of birth,etc. Results: 135 investigator centres out of the 137 initial centres took part. The 2 non-participating centres represented 56 patients. The vital status could be defined for 5441 of the other 5611 patients (97.0%). 88.4% of these patients had died (average time between inclusion and death: 10.5–10.7 months). In univariate study, survival status is linked with age (p < 0.0001), tobacco consumption (p < 0.0001), performance status (p < 0.0001), cancer type (small versus non small cell lung cancer-NSCLC: p < 0.0001) and for the NSCLC, with histological type (p < 0.0001) and TNM stage (p < 0.0001). According to multivariate analysis, survival status is related to age, performance status, cancer type and among the NSCLC, to age, sex, performance status, histological type and TNM stage. Conclusions: The survival study on PBC is the first one in France, including more than 5,400 patients. The first results show the prognosis role of age, sex, histological type, performance status and TNM stage. No significant financial relationships to disclose.
Vorinostat (suberoylanilide hydroxamic acid, SAHA) is clinically active in advanced cutaneous T-cell lymphoma (CTCL): Results of a phase IIb trial
Authors: Olsen E. , Kim Y. H. , Kuzel T. , Pacheco T. R. , Foss F. , Parker S. , Wang J. G. , Frankel S. R. , Lis J. , Duvic M. 
Published: March 2020

7500 Background: Vorinostat is a histone deacetylase inhibitor that has demonstrated clinical activity at tolerable dose levels in patients (pts) with advanced CTCL in phase I and IIa trials. Methods: Open-label, single-arm, nonrandomized phase IIb trial of oral vorinostat 400 mg daily until disease progression or intolerable toxicity. Eligibility: advanced CTCL; ≥ 2 prior systemic therapies which must have included bexarotene unless unable to tolerate; adequate hematologic, hepatic and renal function. Planned sample size: ≥ 50 evaluable pts with clinical stage ≥ IIB. Primary endpoint: objective response rate (OR = CR + PR) as measured by a modified skin severity weighted assessment tool. The study would be positive if OR in ≥ stage IIB pts was ≥ 20%. Secondary endpoints: assessment of response duration (DOR), time to progression (TTP), time to response (TTR), pruritus relief and safety. Results: Seventy-four pts (median age, 60 y [range, 39–83]; median 3 prior systemic therapies) were enrolled (61 pts ≥ stage IIB) from 9/04 to 5/05 at 18 centers. Data cut-off was 11/05 with a median follow-up of 4 months. Efficacy data are shown in Table 1 . The OR was 29.5% (18 PR including 1 with later CR) in ≥ stage IIB pts. Median TTP was 148 d for all pts and 203.5+ d for responders. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%) and anorexia (26%), and were mostly ≤ Grade 2. Drug-related ECG changes were Grade 1 in 5 pts (7%) and Grade 2 in 1 pt (1%), but not associated with cardiac symptoms. Seven pts discontinued and 10 had dose modification due to drug-related AE. Drug-related AE ≥ Grade 3 included fatigue (5%), pulmonary embolism (5%), nausea (4%) and thrombocytopenia (4%). Twenty-five pts discontinued due to progressive disease. Causes of the 3 deaths on study were: unknown (d 2), ischemic stroke (d 227) and disease progression (d 52). Conclusion: Oral vorinostat is effective in the treatment of advanced CTCL with an acceptable safety profile. [Table: see text] [Table: see text]
Mantle cell lymphoma (MCL): Induction therapy with HyperCVAD/High-dose methotrexate and cytarabine (M-C) (±rituximab) improves results of autologous stem cell transplant in first remission
Authors: Vose J. , Loberiza F. , Bierman P. , Bociek G. , Armitage J. 
Published: March 2020

7511 Background: Although patients (pts) with MCL have a high response rate to standard chemotherapy, they continue to relapse with no plateau in long term disease-free survival. The use of dose intense induction therapy such as HyperCVAD (M-C) ±Rituximab(R) and high-dose therapy and stem cell may improve these results. In this analysis the outcomes of pts receiving a standard anthracycline induction therapy or HyperCVAD(M-C)(±R) then followed by a stem cell transplant in first complete (CR1) or partial remission (PR1) were compared. Methods: Between 6/91 and 11/05, 124 pts with MCL received high-dose chemotherapy and a stem cell transplant. Of these pts, 80 received an autologous stem cell transplant in CR1 (N = 47) or PR1 (N = 33). A standard anthracycline based CHOP-like (±R) induction therapy was given to 48 pts compared with 32 pts who received HyperCVAD(M-C)(±R) prior to transplant. Results: The median age of pts was 56 years (range 33–70). The male:female ratio was 33:57. Bone marrow involvement prior to conditioning was present in 52% of pts. An elevated lactic dehydrogenase (LDH) was present in 58% of pts. 65% of patients received one prior chemotherapy before coming to stem cell transplant. The median follow up of pts is 38 months (range 3–143). Progression-free survival (PFS) and overall survival (OS) are outlined in table 1 . Characteristics associated with an improved OS by multivariate analysis included receiving HyperCVAD induction (p = 0.04), transplant in CR1 (p = 0.009), ≤ 3 prior chemotherapy regimens (p = 0.02) and no B symptoms at transplant (p = 0.05). Conclusions: To improve the long term disease free survival for pts with MCL, Hyper-CVAD(M-C)(±R) induction should be given to eligible patients with autolgous stem cell transplantation in CR1. [Table: see text] No significant financial relationships to disclose.
A multicenter, randomized, double-blind, placebo-controlled trial of thalidomide plus dexamethasone versus dexamethasone alone as initial therapy for newly diagnosed multiple myeloma
Authors: Rajkumar S. V. , Hussein M. , Catalano J. , Jedrzejcak W. , Sirkovich S. , Olesnyckyj M. , Yu Z. , Knight R. , Zeldis J. B. , Blade J. 
Published: March 2020

7517 Background: Thalidomide plus dexamethasone (Thal/Dex) yields superior response rates versus dexamethasone (Dex) but its impact as primary therapy for multiple myeloma (MM) is unknown. Methods: Patients (pts) with previously untreated, symptomatic MM were eligible and were randomized in this double-blind trial to Thal/Dex (Arm A) or placebo plus Dex (Arm B). Pts in Arm A received Thal 50 mg PO daily, escalated to 100 mg on day 15, and to 200 mg from day 1 of cycle 2; Dex 40 mg PO was given on days 1–4, 9–12, and 17–20. Pts in Arm B received placebo instead of Thal, and Dex as in Arm A. Cycles were 28 days long, repeated until progression or undue toxicity. The primary endpoint was time to progression (TTP) defined using EBMT criteria. All analyses were intent to treat. Planned sample size was 218 eligible pts in each arm. Full information for one-sided log rank test with significance level of 0.025 (allowing for 1interim analysis) to have 80% power to detect a 40% improvement in TTP (16.8 mo in Arm A vs. 12 mo in Arm B) would be achieved when 282 pts have progressed. A pre-planned interim analysis of the primary endpoint and safety was performed by an independent Data Monitoring Committee (DMC). P value < 0.0015 at this interim analysis would indicate that Arm A is superior to Arm B based on an alpha-spending function of the O’Brien-Fleming type. The DMC recommended release of results. Results: 470 pts were enrolled: 235 randomized to Thal/Dex and 235 to placebo/Dex. Median follow-up was 25 months. Median age was 65 yrs. TTP was significantly superior with Thal/Dex vs placebo/Dex, median TTP 17.4 months (95% CI: 8.1 months-NE) vs 6.4 months (95% CI: 5.6–7.4 months), respectively, P < 0.000065, crossing the upper boundary for superiority. DVT was higher with Thal/Dex vs placebo/Dex, 15.4% vs 4.3%, respectively. Median survival was not reached in either arm. Conclusions: Thal/Dex is significantly superior to Dex alone as first-line therapy for multiple myeloma. [Table: see text] [Table: see text]
Oral lenalidomide plus melphalan and prednisone (R-MP) for newly diagnosed multiple myeloma
Authors: Palumbo A. , Falco P. , Benevolo G. , Canepa L. , D’Ardia S. , Gozzetti A. , Nozza A. , Zeldis J. , Boccadoro M. , Petrucci M. T. 
Published: March 2020

7518 Background: Lenalidomide (Revlimid) is a novel oral immunomodulatory drug active in refractory multiple myeloma (MM). In this multicenter trial, we evaluate the effect of the combination lenalidomide, melphalan and prednisone (R-MP). Methods: Patients (pts) with newly diagnosed symptomatic MM ≥ 65 years received 9 courses of lenalidomide (21 days every 4–6 weeks) plus MP (4 days every 4–6 weeks). The trial was designed to asses toxicity and efficacy of R-MP combination. Four dose levels were tested (table 1). Each cohort included 6 pts, with additional 15 pts in level 3 and 4. Dose limiting toxicity (DLT) was defined as: grade ≥ 3 non-hematologic toxicity; grade 4 hematologic toxicity (with neutropenia lasting >7 days); treatment delay due to toxicity during the first cycle. All pts received ciprofloxacin and aspirin as prophylaxis. Results: At present, 50 pts (median age 71) received at least one R-MP course. No DLTs were observed in levels 1 and 2. In level 3, 1 pt experienced DLT (grade 4 neutropenia > 7 days). In level 4, 3 pts showed DLTs (neutropenic fever, grade 3 cutaneous toxicity, pulmonary embolism and cycle 2 delay due to neutropenia). After 1 cycle, no one was in complete remission (CR) (according to the EBMT/IBMTR criteria), 51% of pts showed a response of 50–99% (PR) and 49% a response <50%, no progressive disease (PD) occurred. After 3 cycles, CR was observed in 10% of pts, PR in 60% and response <50% in 30%, no PD occured. Major grade 3–4 adverse events were hematological toxicities: neutropenia (58%) and thrombocytopenia (21%). Major grade 3–4 non-hematological toxicities were cutaneous eruption (11%), infections (5%) and febrile neutropenia (3%). Neuropathy was not observed and only one thromboembolism was recorded. Conclusions: R-MP was well tolerated with a manageable toxicity. Significant response rate was observed. It represents a feasible and promising approach for elderly newly diagnosed pts. An update of these data will be presented. [Table: see text] [Table: see text]
Preliminary immune response (IR) results of a phase 2 study with idiotype (Id) immunotherapy after treatment with CVP and rituximab for follicular non-Hodgkin’s lymphoma (FL)
Authors: Leonard J. P. , Mason K. , Theriault T. , Milner K. , Sornasse T. , Ingolia D. , Mayo M. , Denney D. W. 
Published: March 2020

7529 Background: Idiotype (Id) is a collection of unique immunogenic epitopes present on the surface of malignant B cells. Keyhole limpet hemocyanin (KLH) is a carrier protein used to increase antigen immunogenicity. MyVax Personalized Immunotherapy consists of the patient- and tumor-specific Id protein, produced using molecular techniques, conjugated to KLH and administered in a series of subcutaneous immunizations with the adjuvant GM-CSF. Idiotype vaccines were first studied in combination with various chemotherapeutic agents as part of initial treatment for FL. Given the widespread usage of rituximab in treating FL, the nature of IRs in patients immunized with MyVax Personalized Immunotherapy following rituximab treatment are of interest. CD19+ B cell counts following treatment with rituximab were analyzed for correlation with patient-specific Id-KLH induced humoral IR data. Methods: In a Phase 2 study, MyVax Personalized Immunotherapy following rituximab is being evaluated for patients who failed to achieve at least a PR and maintain the response over a 6 month rest period after 8 cycles of CVP chemotherapy. Eligible patients received 4 weekly doses of rituximab followed by a 13 or 26 week rest period. Patients who achieved and maintained a PR or better then received 8 immunizations with MyVax Personalized Immunotherapy over 14 weeks. CD19+ B cells and humoral IRs against Id and KLH were monitored during and 2, 8, 20, 32, 44 and 56 weeks post-immunizations. Results: 87 pts received rituximab. 52 pts went on to immunization. Median CD19 counts for all arms of the study were lower post-rituximab treatment (pre-treatment median = 76 cells/ul (N = 57) vs. post-treatment = 13 cells/ul (N = 51 evaluable); p < 0.0001). Positive results are defined as a titer >0.1 mcg/ml. 49/52 (94%) evaluable pts were able to mount anti-KLH humoral IRs post rituximab. The magnitude of the anti-KLH response was generally greater in pts with higher B cell counts when beginning immunizations. Anti-Id IRs were also observed. Conclusions: Humoral IRs to KLH occur in pts receiving MyVax Personalized Immunotherapy and correlate with regeneration of B cells post-rituximab but appear less robust than in rituximab-naïve pts. [Table: see text]
Efficacy of radioimmunotherapy with (90Y) ibritumomab tiuxetan is superior as consolidation in relapsed or refractory mantle cell lymphoma: Results of two phase II trials of the European MCL Network and the PLRG
Authors: Weigert O. , Jurczak W. , Von Schilling C. , Giza A. , Rummel M. , Hubalewska A. , Pezzutto A. , Unterhalt M. , Hiddemann W. , Skotnicki A. , Dreyling M. 
Published: March 2020

7533 Background: Radioimmunotherapy (RIT) has demonstrated high clinical efficacy in follicular lymphoma but varying results in mantle cell lymphoma (MCL). Methods: We performed a comparative analysis of two phase II studies with similar inclusion criteria to identify potential predictors of response. 32 patients with relapsed or refractory MCL, WHO performance status ≤2, appropriate hematopoesis (ANC > 1,500/mm3, platelets > 100,000/mm3) and adequate function of liver and kidneys were treated with RIT upfront (Arm A, n = 16) or as consolidation after initial cytoreduction (Arm B, n = 16). 28 patients (88%) had been previously treated with rituximab. Patients with >25% bone marrow involvement, known CNS lymphoma, HIV infection or other severe concurrent disease were excluded. Ibritumomab tiuxetan (Zevalin) was applied at a dose of 15 MBq 90Y/kg, whereas patients with reduced platelet counts (<150,000/mm3) received 11 MBq 90Y/kg. Results: The median age was 66.9 years (range 58–72) in Arm A and 63.1 years (range 45–79) in Arm B. The median number of prior regimens was 4 (range 2–6) in Arm A and 1 (1–5) in Arm B. RIT treatment was generally well tolerated with the most common toxicities being hematologic. Thrombocytopenia grade 3 and 4 was observed in 69% of patients, one patient died of hemorrhagic stroke. Granulocytopenia grade 4 occurred in 34% of patients, one patient developed a grade 4 infectious complication. Currently 22 patients are evaluable for response rate and duration of remission (DR). In Arm A a partial response (PR) was observed in 2 of 6 evaluable patients (33.3%) with a median DR of 3.9 months only. In Arm B chemoinduction achieved 2 complete responses (CR) and 14 PR. Following RIT seven of 14 PR patients (50%) converted to CR. Currently, 13 of 16 patients (81%) are still in remission. As expected the most important adverse risk factor was bulky disease before RIT with no responses seen in this patient population. Patients with less prior therapeutic lines (< 2) had significantly higher response rates. Conclusions: In future trials, RIT should be applied earlier in the treatment algorithm of MCL after a debulking strategy with combined immuno-chemotherapy. [Table: see text]