bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity of refractory hairy cell leukemia to BRAF inhibition.
Authors: Dietrich Sascha , Lehners Nicola , Huellein Jennifer , Andrulis Mindaugas , Hundemer Michael , Jethwa Alexander , Capper David , Froehling Stefan , Kalle Christof V. , Ho Anthony D. , Glimm Hanno , Zenz Thorsten
Published: March 2020

6519

Background: Thorough understanding of genetic lesions in cancer and targeted intervention against driver mutations are beginning to transform cancer treatment. An activating mutation of the BRAF serine/threonine protein kinase, BRAF V600E occurs in a proportion of malignant melanomas, and colorectal, thyroid, and other cancers. In hairy-cell leukemia (HCL), BRAF V600E is nearly always present, suggesting oncogene dependence. Methods: Here, we present a patient with HCL who was refractory to three lines of purine analogue-based treatment. The BRAF V600E mutation was demonstrated. After intensive counseling, the patient and his family provided written consent for vemurafenib (mutant BRAF-specific inhibitor) treatment. Results: Before vemurafenib treatment, the patient had subtotal bone marrow infiltration and massive splenomegaly (24.8 x 8.3 cm) leading to severe cytopenia (leukocytes 680/µl, hemoglobin 10.0 g/dl, platelets 36.000/µl). Treatment with vemurafenib was started with 240 mg twice daily and was slowly escalated to 1920 mg/d. Within two days of treatment, the spleen softened and decreased in size. Serum CD25 (sCD25) level fell rapidly from 24.800 U/ml to normal levels (<900), and platelets, hemoglobin, and leukocyte counts rose. After 16 days of vemurafenib treatment, the spleen size had shrunk to 14 x 5 cm. By day 28 of treatment (on 720 mg/d), platelet counts and sCD25 levels had normalized. Bone marrow infiltration by HCL had decreased from 70% to 20% on day 16 and complete remission was achieved on day 35. We terminated treatment on day 57 when there was no evidence of any circulating hairy cells by immunophenotyping. Conclusions: The striking therapeutic activity of vemurafenib in our patient provides the first in vivo evidence to substantiate the BRAF V600E allele as a driver and validates mutant BRAF as a therapeutic target in HCL. Proof of principle for a molecularly targeted therapy of HCL adds to the recent success of targeting oncogenic kinases in oncogene addicted malignancies. Given the rarity of HCL, introducing new therapeutic modalities may be challenging. Future studies are needed that compare short-term inhibition of BRAF with low doses of vemurafenib (or alternative BRAF inhibitors) and standard therapy.
Prognostic implication of monosomal karyotype in patients with acute myeloid leukemia who received allogeneic hematopoietic cell transplantation.
Authors: Choi Yunsuk , Kim Sung-Doo , Park Young-Hun , Lee Jae Seok , Kim Dae-Young , Lee Jung-Hee , Lee Kyoo-Hyung , Seol Miee , Lee Young-Shin , Kang Young-Ah , Jeon Mijin , Jung Ah Rang , Lee Je-Hwan
Published: March 2020

6564

Background: Monosomal karyotype (MK), defined as at least two autosomal monosomies or one single autosomal monosomy with one or more structural cytogenetic abnormalities, has been associated with worse outcomes in acute myeloid leukemia (AML). We evaluated the prognostic impact of MK on outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) in AML. Methods: We retrospectively analyzed 169 adult patients with AML, who received allo-HCT in the first complete remission (CR) between 2000 and 2009. All patients had cytogenetic results at the diagnosis of AML. Patients were classified as having good, intermediate, or poor risk cytogenetics according to the NCCN guideline, and MK status was also determined. Results: MK was observed in 12 patients (7.1%); of whom, 11 patients also had complex karyotype (CK). Compared to patients without MK, those with MK had significantly lower overall survival (OS) (62.2% vs. 0%) and event free survival (EFS) (58.9% vs. 0%), and higher relapse probability (RP) (22.9% vs. 66.7%) at 5 years (all, p<0.001). 22 patients with CK also showed inferior outcomes, but CK with MK was associated with more inferior outcomes than CK without MK. Multivariate analysis showed that MK had a significantly adverse impact on OS (hazard ratio [HR], 5.192; p<0.001), EFS (HR, 4.531; p<0.001), and RP (HR, 6.558; p<0.001) after allo-HCT (Table). Conclusions: MK is a major prognostic factor predicting extremely worse outcomes in AML patients who underwent allo-HCT in the first CR. [Table: see text]
Interim results of a phase I/II randomized study of clofarabine, idarubicin, and cytarabine (CIA) versus fludarabine, idarubicin, and cytarabine (FIA) for newly diagnosed or relapsed patients (pts) with acute myeloid leukemia (AML).
Authors: Mathisen Michael , Kantarjian Hagop , Faderl Stefan , Garcia-Manero Guillermo , Ravandi Farhad , Kadia Tapan M. , Daver Naval Guastad , O'Brien Susan Mary , Dorkhom Stephan Joseph , Pierce Sherry , Lira Cynthia , Cortes Jorge E. , Jabbour Elias
Published: March 2020

6607

Background: Outcomes of pts with AML remain suboptimal. The addition of cladribine to 3+7 has been shown to improve complete remission (CR) rates and 3-year survival. The aim of this study was to assess the efficacy and safety of idarubicin + cytarabine (IA, idarubicin 10 mg/m2 on days 1-3, cytarabine 1 g/m2 on days 1-5) combined with two other nucleoside analogs, clofarabine (C) or fludarabine (F), in pts with newly diagnosed and relapsed/refractory (RR) AML. Methods: Pts with newly diagnosed or RR non-M3 AML with normal organ function were eligible. Pts with RR disease were treated in the phase I portion defining the MTD of C. The starting dose of C was 15 mg/m2 with doses escalating to 25 mg/m2 on days 1-5 in subsequent cohorts. During phase II, patients were randomized in a Bayesian design to C at the MTD with IA or fludarabine (F) at 30 mg/m2 on days 1-5 with IA. Up to 6 consolidation cycles were planned according to an attenuated schedule using the same drugs. Dose adjustments were made for elderly pts or pts with poor PS. Results: 9 pts were enrolled in the phase I portion. The overall response rate (ORR) in this group was 44%. DLT were observed at C 20 mg/m2 and included hand/foot syndrome (HFS), elevated bilirubin, and prolonged myelosuppression. The MTD was 15 mg/m2 on days 1-5. 50 evaluable pts were enrolled (16 newly diagnosed, 34 RR) in the phase II. In the frontline cohort, median age was similar in both groups (C 56, F 55), as were the cytogenetic profiles. The CR rate was 100% in both groups (9 CIA, 7 FIA). Detailed efficacy information can be found in the Table. More than half of the RR cohort were receiving therapy as salvage 2 or higher, and most had short first CR durations. Notable toxicities included elevated liver function tests for both groups, and HFS in the C group. There were 4 deaths on study, though most pts were receiving therapy as second salvage and were over the age of 60. Conclusions: CIA and FIA are effective regimens for newly diagnosed or RR AML with manageable toxicity profiles. The ORR were 100% and 32% for newly diagnosed and RR AML pts, respectively, with low early mortality rates. The study is ongoing.
Post hoc analysis of relationship between baseline white blood cell count and renal and hepatic function and response in a randomized phase III trial of decitabine in patients age 65 or older with acute myeloid leukemia.
Authors: Delaunay Jacques , Mazur Grzegorz , Minden Mark D , Wierzbowska Agnieszka , Jones Mark M. , Tarassoff Peter G. , Kantarjian Hagop
Published: March 2020

6632

Background: A phase III trial (NCT00260832) in patients (N=485) ≥65y with newly diagnosed acute myeloid leukemia (AML) was conducted (Kantarjian, JCO; in press). Every 4 wk, patients received decitabine (DAC) 20 mg/m2 (1-h intravenous infusion, 5 successive days) or treatment choice (TC) with either supportive care or cytarabine (20 mg/m2 subcutaneous injection daily, 10 successive days). This post hoc analysis examined whether baseline (BL) renal and hepatic function and white blood cell (WBC) counts were associated with response to DAC or TC. Methods: For patients with available data, BL WBC count and markers of renal function (blood urea nitrogen [BUN], creatinine) and liver function (ALT, AST, albumin) were tabulated for patients with/without a response to DAC or TC. Response was defined as morphologic complete remission (CR), CR with incomplete blood count recovery (CRi), or partial remission (PR). Results: Nonresponders had a higher mean BL creatinine vs responders (86.78 vs 80.23 mmol/L, respectively; P=.005); with no differences in BL BUN levels. There were no other between-group differences. Conclusions: This analysis suggests that there is no relationship between BL WBC or hepatic function and response to treatment with DAC or TC. Although there was no difference in BL BUN, higher mean creatinine levels in nonresponders may suggest a prognostic relationship but further studies are needed to clarify. [Table: see text]
High-throughput targeted resequencing of lung adenocarcinoma.
Authors: Kim Byung Chul , Kim Eun-Hye , Ghim Byoung-Chul , Choi So-Jung , Lee Jinseon , Kim Jhingook
Published: March 2020

7053

Background: The mutational profiles are crucial for cancer diagnosis and classification, which lead to tailoring the best therapeutic strategy to each patient. Here, we present target sequencing of 30 hot spot genes in lung adenocarcinoma to identify new hot spot mutations in never-smoker, female lung adenocarcinoma patients. Methods: We targeted 30 genes that are known to be mutated frequently in lung adenocarcinoma. The exome capture was done using selector technology and sequencing was done using Illumina GA IIx Genome Analyzer. Exomic short reads from Illumina Pipeline 1.4 were aligned to human genome (NCBI build 36) with BWA 0.5.0. Variations and small indels were called by Samtools 0.1.7 and filtered by custom R scripts. Potential effects of these identified alterations were assessed with sequence analysis. Results: On average, 1.5 billion bases were uniquely mapped, and mean depth and coverage of exon regions were 38X and 96%, respectively. Filtering of data against public SNP database (dbSNP130), resulted in ~2,000 novel genetic alterations per sample, including single nucleotide variations, and small insertion and deletions in protein-coding regions. Among them, there were novel variants in LTK and EPHA5 genes. Conclusions: Our results demonstrated the feasibility of high-throughput mutation profiling with lung adenocarcinoma samples. We identified novel variants in hot target genes, which may provide an insight into the tumorigenesis signaling of lung adenocarcinoma.
Are the presenting characteristics and prognosis of primary salivary gland-type lung cancers (SG) similar to those of other non-small cell lung cancers (NSCLC)?
Authors: Varlotto John M. , Ali Suhail M. , DeCamp Malcolm M. , Flickinger John Charles , Recht Abram , Lake Jessica , Ramakrishna Satvik , Lipton Allan , Zander Dani , Reed Michael , Toth Jennifer , Belani Chandra Prakash
Published: March 2020

7054

Background: SG, both adenoid cystic (ACC) and mucoepidermoid (ME) sub-types, are rare lung cancers. We choose to investigate the incidence of these rare sub-types and assess their difference in presentation and prognostic characteristics in comparison to adenocarcinomas (Ad) and squamous cell carcinomas (SCC) during the same time period. Methods: The SEER-17 database was used to collect data during the years 1988-2008. Differences between populations were determined by the chi-square test. Survival curves were generated as Kaplan-Meier techniques. Cox proportional hazards test was used to compare survival differences. Results: During the 20-year study period, ACC (n =100) and ME (n= 178) accounted for 0.03% and 0.06% of NSCLCs. Mean follow-up was 34.5 months for all patients. In comparison to ACC, patients with ME were significantly more likely to be younger (52 yr vs. 60yr), Asian(11.7% vs. 7%), have Stage I disease (62.9% vs 24.0%), and less likely to be in the mainstem bronchi (17.2% vs. 6.3%). In comparison to patients with patients presenting with either SCC or Ad, both ME and ACC were significantly less likely to present with Stage IV disease (26.6% SCC, 41.29% Ad, 16.73% SG), have nodal involvement (35.1% SCC, 27.4% Ad, 23.37% SG), and be older (70 SCC, 68 Ad, 58 years SG). Stratified by stage and treatment, there was no survival (OS) or disease-specific survival difference (DSS) between ACC and ME. The OS of the combined group of ME and ACC was significantly better stage per stage than either Ad (Hazard ratio (HR) range = 0.26- 041), and SCC (HR range = 0.17-0.56). Lung Cancer-Specific survival at 2,3,5 years for surgically-resected Stage I ACC and ME were 83.5%, 80.4%, and 80.4%; and 82.6%, 78.0% and 78%, respectively. Conclusions: Patients with ACC and ME have rare sub-types of lung cancer that present differently and have better survival than patients presenting with either of the more common histologic sub-types (SCC and Ad) of NSCLC. We encourage prospective, multi-institutional studies of these rare sub-types so that care can be optimized. Optimal care may differ for SG because of their stage per stage better prognosis than other NSCLCs.
NGR-hTNF as second-line treatment in malignant pleural mesothelioma (MPM).
Authors: Rossoni Gilda , Gregorc Vanesa , Viganò Maria Grazia , Bulotta Alessandra , Ghio Domenico , Lambiase Antonio , Bordignon Claudio
Published: March 2020

7076

Background: NGR-hTNF exploits the asparagine-glycine-arginine (NGR) peptide for selectively targeting tumor necrosis factor (TNF) to cancer endothelial cells. Tumor hypervascularity is an independent predictor of poor overall survival (OS) in MPM patients (pts). Methods: We report long-term results of a phase II trial that assessed NGR-hTNF in MPM pts with performance status (PS) ≤ 2 and radiologic progressive disease (PD) after a pemetrexed-based regimen. NGR-hTNF was given at 0.8 µg/m2 every 3 weeks (q3w) in 43 pts and weekly (q1w) in 14 pts. Primary endpoint was progression free survival (PFS), with restaging done q6w by MPM-modified RECIST criteria, while secondary aims included disease control (DC) rate and OS. We also tested the impact on outcome of neutrophil to lymphocyte ratio (NLR) at baseline (median 3; interquartile range 2-5). Median follow-up was 32.5 months (95% CI 27.5-37.5). Results: Baseline characteristics were (n=57): median age 57 years; M/F 35/22; PS 0/1-2 31/26; EORTC score good/poor 45/12. Median treatment free interval on prior therapy was 4.3 months. Only one drug-related grade ≥ 3 adverse events (AEs) was noted, common grade 1/2 AEs being transient chills (75%). No higher toxicity was reported using the q1w schedule. Median PFS was 2.8 months (95% CI 2.2-3.3). DC rate was 46% (95% CI 32-59; 26/57 pts; 1 partial response, 25 stable diseases) and was maintained for a median time of 4.7 months (95% CI 4.0-5.4). OS rates at 1 and 2 years were 47% and 16%, respectively. Median OS was longer in pts with DC than in those with early PD (16.2 and 8.3 months, respectively; p=.02). According to schedule, 6-month PFS rates were 11% and 36% and 2-year OS rates were 12% and 29% for q3w and q1w, respectively. In pts with DC, median PFS were 4.4 and 9.1 months and median OS were 13.3 and 24.8 months for q3w and q1w, respectively. By Cox analyses, a PS of 0 (p=.01) and a low baseline NLR (p=.004) were the only variables associated with improved OS. Median OS in pts stratified by NLR ≤ 2, 3 to 4, and ≥ 5 were 15.7, 10.5, and 4.2 months, respectively (p=.0002 for trend). Conclusions: NGR-hTNF showed promising PFS and OS in this study. A double-blind phase III trial is currently testing best investigator choice ± NGR-hTNF q1w in pemetrexed-pretreated MPM pts (NCT01098266).
Comparison of treatment patterns, health care utilization, and direct costs in elderly patients with distant-stage small cell lung cancer (SCLC) versus non-small cell lung cancer (NSCLC) using the SEER-Medicare database.
Authors: Karve Sudeep , Price Gregory , Davis Keith L. , Pohl Gerhardt , Smyth Emily Nash
Published: March 2020

7101

Background: Limited data exist on real-world treatment patterns, healthcare utilization, and associated costs of advanced SCLC among elderly patients in the US, and there are no recent comparisons between patients with advanced SCLC and advanced NSCLC. Methods: We retrospectively analyzed administrative claims data for elderly patients (≥65 years) from the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database for 2000-2008. Patients with a new diagnosis of distant stage lung cancer receiving cancer-directed therapy (ie, surgery, radiation, biologics, and/or chemotherapy) were grouped by tumor type (SCLC [n=5,855] vs NSCLC [n=24,090]). Survival was compared using Kaplan-Meier Log-rank; categorical measures with Chi-square statistics; and continuous measures with t-tests. Results: Compared to SCLC patients, a significantly greater proportion of patients with NSCLC received radiation therapy (75.6% vs 65.4%; p<0.001) and surgery (13.6% vs 7.8%; p<0.001). Chemotherapy was received by 85.5% of SCLC patients and 60.3% of NSCLC patients (p<0.001). Significantly higher proportions of SCLC patients also received red blood cell (20.7% vs 10.9; p<0.001) and platelet transfusions (5.6% vs 1.8%; p<0.001) as well as growth factor support (58.9% vs 39.5%; p<0.001). Survival did not differ significantly between groups (p=0.424), with the mean (10.4 months vs 11.1 months) and median (7.4 months vs 5.9 months) survival for SCLC and NSCLC noted accordingly. Total lifetime lung cancer-related costs ($44,167 vs $37,932; p<0.001) and all-cause costs ($70,548 vs $67,175; p<0.001) per patient for SCLC exceeded those for NSCLC. The primary drivers of cost included resource utilization across 3 care settings: hospitalizations, office visits, and hospital outpatient visits. Conclusions: Overall total lifetime and disease-related costs per advanced SCLC and NSCLC patient were high, and costs for SCLC exceeded those for NSCLC. Survival estimates coupled with per patient costs for both cancers underscores the unmet medical need for patients with distant stage SCLC and NSCLC.
Phase II study of the HSP90 inhibitor AUY922 in patients with previously treated, advanced non-small cell lung cancer (NSCLC).
Authors: Garon Edward B. , Moran Teresa , Barlesi Fabrice , Gandhi Leena , Sequist Lecia V. , Kim Sang-We , Groen Harry J.M. , Besse Benjamin , Smit Egbert F , Kim Dong-Wan , Akimov Mikhail , Avsar Emin , Bailey Stuart , Felip Enriqueta
Published: March 2020

7543

Background: AUY922 is a highly potent, non-geldanamycin, HSP90 inhibitor. A Phase I study in advanced solid tumors provided a recommended Phase II dose of 70 mg/m2. HSP90 acts as a chaperone of client proteins, including those relevant in NSCLC pathogenesis. This Phase II study assessed AUY922 in pts with previously treated advanced NSCLC stratified by molecular status. Methods: Pts with advanced NSCLC who progressed following ≥2 prior lines of chemotherapy, received AUY922 70 mg/m2 as a 1-hr infusion once-weekly. Pts were assigned to 4 strata: EGFR activating mutations (EGFR mut), KRAS mut, ALK rearranged (ALK+), or EGFR/KRAS/ALK wild type (wt). Phase II Bayesian hypothesis testing design allowed sharing of information between strata based on assessing similarity in observed response data. Primary endpoint was confirmed (RECIST) objective response rate (ORR) or stable disease (SD) at 18 wks. Secondary endpoints included OS, PFS, and safety/tolerability. Results: A total of 112 pts (median age 60 years; 45% male; 86% adenocarcinoma; 28 [25%] pts KRAS mut; 35 [31%] EGFR mut; 14 [12%] ALK+; 31 [28%] EGFR/KRAS/ALK wt) were treated at the December 16th 2011 cutoff. Most pts were heavily pretreated: 61% had received ≥3 prior systemic regimens; 64% had WHO PS 1 or 2. Mean duration of exposure was 9.1 wks. The most frequent adverse events (AEs, any grade [Gr]) were diarrhea (73%), visual AEs (71%), and nausea (43%). Most AEs were Gr 1/2; Gr 3/4 AE’s were rare (all <10%). The study is ongoing, and 29 pts were still receiving treatment at the cutoff date. Preliminary clinical activity of AUY922 (RECIST; investigator assessed) was seen with partial responses in 13/101 (13%) pts: 2/8 (25%) ALK+ pts, 6/33 (18%) EGFR mut pts, 4/30 (13%) EGFR/KRAS/ALK wt pts, 0/26 (0%) KRAS mut pts, and 1/4 (25%) pts of unknown status. In ALK+ pts, responses were seen in crizotinib (CRZ)-naive pts, and SD was seen with tumor shrinkage in CRZ-resistant pts. PFS data will be presented. Conclusions: AUY922 had an acceptable safety profile and demonstrated preliminary activity in heavily pretreated pts with advanced NSCLC. This trial demonstrates clinical activity of AUY922 in EGFR mut and EGFR/KRAS/ALK wt NSCLC pts in addition to ALK+ pts.
Afatinib monotherapy in patients with metastatic squamous cell carcinoma of the lung progressing after erlotinib/gefitinib (E/G) and chemotherapy: Interim subset analysis from a phase III trial.
Authors: Kim Joo-Hang , Grossi Francesco , De Marinis Filippo , Cobo Manuel , Yang James Chih-Hsin , Ragulin Yury , Bondarenko Igor N. , Chand Vikram K. , Wang Bushi , Gracien Edith , Schuler Martin H.
Published: March 2020

7558

Background: Patients with squamous NSCLC have limited treatment options. For those deriving benefit from EGFR TKIs, it is unclear whether sustained ErbB family blockade offers benefit upon progression. We evaluated afatinib, an irreversible blocker of EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptor tyrosine kinases, in patients with metastatic NSCLC who had failed chemotherapy and E/G. Here we describe a pre-specified analysis of those with squamous histology in Part A. Methods: This randomized Phase III, open-label, multi-center trial enrolled patients with pathologically confirmed metastatic NSCLC after failing ≥1 line of cytotoxic chemotherapy and E/G. In Part A, patients received oral afatinib 50 mg until disease progression. Those with clinical benefit (≥12 wks) who progressed were eligible to receive afatinib plus paclitaxel or investigator’s choice chemotherapy (Part B). Primary endpoint was PFS (RECIST 1.1). Following an amendment, an interim analysis of Part A was performed to assess afatinib monotherapy. Results: Patient enrolment into Part A was from April 2010 to May 2011. Of 1154 afatinib-treated patients, 91 (8%) had squamous histology; 18/91 and 40/91 had CR/PR and SD on prior E/G, respectively (by investigator). Median age was 63 yrs, 71% were male, 76% were current/ex-smokers. Median PFS on afatinib was 3.7 mths in the squamous histology subset. Of 91 patients, 42 had PFS ≥3 mths; 13 had PFS of ≥6 mths. In evaluable patients (n=77), 1 CR and 3 PRs were confirmed; 51 and 22 patients had best overall response of SD and PD, respectively. Of the 31 patients with PD on prior E/G with no intervening chemotherapy, 10 achieved confirmed disease control (2 PR; 8 SD) on afatinib. Most commonly reported grade 3/4 adverse events (AEs) in Part A were diarrhea (13%) and rash/acne (12%). The safety profile in the squamous histology subset was similar to that observed for the whole trial. Conclusions: Afatinib monotherapy demonstrated encouraging activity in treatment-refractory NSCLC patients with squamous histology that merits further evaluation.
Multicenter, phase II study of bendamustine in refractory or relapsed T-cell lymphoma: The BENTLY trial.
Authors: Gressin Remy , Damaj Gandhi Laurent , Bouabdallah Kamal , Cartron Guillaume , Choufi B , Gyan Emmanuel , Jaccard Arnaud , Park Sophie , Schiano De Colella Jean-Marc , Voillat Laurent , Joly Bertrand , Le Gouill Steven , Saad Alain , Sanhes Laurence , Moles-Moreau Marie-Pierre , Bubenheim Michael , Bene Marie C. , Martin Antoine , Marolleau Jean pierre , Lamy Thierry
Published: March 2020

8026

Background: T-cell lymphomas have a poor prognosis with few options of effective treatment. This study determined the efficacy and safety of bendamustine as a single agent in the treatment of refractory or relapsed T-cell lymphomas. Methods: Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL), who had previously received at least one line of chemotherapy were selected. Bendamustine was administered IV at the dosage of 120 mg/m2 on days 1 and 2 every 3 weeks, for 6 cycles. Treatment response was assessed using the IWC for non-Hodgkin's lymphoma. The primary end point was overall response rate (ORR). Secondary end points were duration of response (DoR), progression-free survival (PFS), and overall survival (OS), NCT00959686. Results: Twenty two female and 38 male were included. The median age was 66 years with more 1/4 of them > 75. Histology was predominantly angio-immunoblastic lymphadenopathy (n=32) and PTCL-nos (n=23). The median previous line of chemotherapy was 1 (1-3). Nearly one half (45%) of the patients was refractory to the last previous chemotherapy and the median duration of the best previous response was 6.6 (1.5-67) months. The disease was disseminated in the majority of case (87%) and the international prognostic index (IPI) was high (3–5) in 68% of the patients. Twenty patients (33%) received less than 3 cycles of bendamustine. The major reason for early discontinuation was disease progression. In the Intent-To-Treat (ITT) population, the best ORR was 50%, including complete response (CR) in 28% and partial response (PR) in 22 %. Bendamustine showed a consistency in the efficacy as a function of major disease characteristics. The median values for DoR, PFS and OS were 3.5, 4 and 6 months respectively. The most frequent grade 3/4 AEs were neutropenia (30%), thrombocytopenia (24%) and infections (20%). Conclusions: Bendamustine is active in high risk refractory and relapsed T-cell lymphoma with manageable toxicity.
Survival with splenectomy in splenic marginal zone lymphoma: Analysis of the Surveillance, Epidemiology and End Results (SEER) database.
Authors: Olszewski Adam J.
Published: March 2020

8044

Background: The role of splenectomy as the primary therapy for splenic marginal zone lymphoma has been questioned. We studied relative survival in SMZL and the impact of splenectomy on lymphoma-specific survival (LSS). Methods: SMZL cases (diagnosed in 1993-2008) were derived from the SEER database. Age, sex and race-matched actuarial survival data were summarized. Factors predictive of splenectomy were studied using logistic regression with a subsequent propensity score (PS)-weighted survival analysis. Results: 1071 patients were identified with a median age of 69 years (range, 25-96) and a median follow up of 33 months. 53% were women and 92% were white. 70% of the lymphomas were stage III/IV with B symptoms recorded in 22.3%. 54% of patients underwent splenectomy. The significant factors predictive of surgery included younger age (p<10-14), stage I/II (p<10-15), B-symptoms (p=0.003), no prior malignancy (p=0.002), with significantly lower rates in black patients (OR 0.41, 95%CI 0.21-0.80, p=0.008), on the Pacific Coast (OR 0.62, 95%CI 0.47-0.81, p=0.0004) and with decreasing rates over time (p=0.0002). The actuarial 5-year relative survival was 82.8% (95%CI 77.9-86.7%) with no difference by sex (p=0.79), race or stage. 54% of deaths were related to SMZL with the estimated LSS of 80.8% (95%CI 78-84%). Splenectomy was not associated with improved LSS in propensity score-stratified log-rank test (p=0.60) or in the PS-weighted Cox model (HR=0.93, 95%CI 0.62-1.38, p=0.70). Advancing age (HR 1.05, 95%CI 1.03-1.07, p<10-8) and presence of B-symptoms (HR=1.98, 95%CI 1.30-3.01, p=0.002) were significantly predictive of death from SMZL, with no evidence of improvement in LSS over the years (HR=0.97, 95%CI=0.91-1.03, p=0.34). There was also no detectable impact of splenectomy on survival in patients who ultimately died of SMZL (p=0.83). Conclusions: In this cohort, the largest studied to date, splenectomy did not demonstrate a survival benefit in SMZL. Patients continue to have decreased survival despite advances in other indolent B-cell lymphomas. The role of splenectomy versus chemoimmunotherapy remains to be determined.
Radioimmunotherapy efficiency and safety in consolidation and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: An updated analysis of 230 patients of the international RIT-network.
Authors: Hohloch Karin , Lankeit Henrike Katharina , Zinzani Pier Luigi , Lorsbach Michael , Windemuth-Kiesselbach Christiane , Trumper Lorenz H.
Published: March 2020

8052

Background: In aggressive lymphoma, few reliable clinical data about the use of radioimmunotherapy exist. Pts. with DLBCL registered in the international RIT-Network (RIT-NT) were analyzed with regard to Indication, line of therapy and outcome. Methods: The RIT-NT recruited 1111 pts. between Dec. 2006 and 2010. It is a web-based registry that collects observational data from RIT-treated patients with malignant lymphoma. 232 pts. with DLBCL registered in the database were evaluated in the analysis. Results: 232 pts with DLBCL are registered, 17 pts were excluded. Histologic subtypes: 190 DLBCL, 15 primary mediastinal, 9 large cell anaplastic, 1 intravascular. Median age was 62 years (range 17-88), 27% of pts >70 years old. Stage I 16pts, II 54 pts, III 60 pts, IV 68 pts; 6 extranodal involvement, for 11 pts. stage is not documented. 187 pts had 1-3 previous chemotherapies (Ctx), 21 pts 4-6 previous Ctx, 1 pts had 7 previous Ctx, for 6 pts. previous Ctx is not documented. 15 pts. had previous RIT and 24 pts a stem cell transplantation prior to RIT. 6 pts had bone marrow infiltration prior to RIT, 3 with more than 25%. 87 pts had RIT as first line (8 pts. conditioning, 68 pts consolidation, 1 primary therapy, 10 other), and 84 pts received RIT in relapse (2d to 8 th. line therapy) (2 pts. conditioning, 31 pts consolidation, 26 recurrence, 19 therapy refractory, 6 other). Grade IV° hematotoxicity occured for neutrophils and platelets, grade III° for hemoglobin after RIT. Median time to recovery of blood count was 81 days (range 0-600 days). ORR was 63,3 %; CR 54,4%; PR 8,8%, SD 0,9%, PD 23,7%, N.D. 12%. CR rate first line was 76,3 %, for relapse 44,3%. Mean overall survival (OS) in first line was 26,5 months 14,3 months for pts. treated in relapse or refractory disease. Conclusions: Most pts. with DLBCL in the RIT-N received RIT as consolidation after first line therapy with excellent CR rates and OS compared to published data from risk groups . In relapsed DLBCL RIT is a safe and feasible treatment leading to satisfactory response rates with low toxicity. A prospective randomized phase III trial in front line DLBCL is currently planned (ZEST).
Use of the cumulative amount of serum-free light chains (sFLC) at diagnosis and PET2 for the early identification of high risk of treatment failure in Hodgkin lymphoma (cHL).
Authors: De Filippi Rosaria , Morabito Fortunato , Corazzelli Gaetano , Russo Filippo , Calemma Rosa , Iaccarino Giancarla , Crisci Stefania , Frigeri Ferdinando , Capobianco Gaetana , Volzone Francesco , Tripodo Claudio , Pinto Antonio
Published: March 2020

8083

Background: Since early identification of patients (pts) at risk of failure is the mainstay of a risk-adapted therapy, we explored the prognostic impact of the sFLC assay in cHL, whose biology involves ongoing activation of polyclonal B-cells. Methods: Serum samples from 248 untreated cHL pts were tested by the Freelite assay. Median age was 32 yrs (r 15-85), males 47%, stages: I (5%), II (51%), III (17%), IV (27%); B-sympt. 60%, E-disease, 38%; bulky >10 cm, 44%; ESR > 65, 42%; IPS ≥3, 39%. Early unfavorable disease (GHLSG/ EORTC) was respectively found in 33% and 42% of cases. ABVD was given to 89% of pts. Results: Absolute FLC levels were summed into a sFLC(κ+λ) variable and ROC analysis indicated 57.1 mg/mL as the threshold to discriminate outcomes. CR rates were 96% and 67% for pts below and above the cutoff, respectively (p<.0001). Cox univariate analysis disclosed a HR of 16.70 (95% CI, 8.5-32.9) of events for sFLC(κ+λ) ≥ 57.1 mg/mL, by far higher than for PET2 positivity (HR 10.8), PS >1 (HR 4.2), IPS ≥3 (HR 2.8) and all other predictors (HR 0.54-2.4). In a multivariaye model only sFLC(κ+λ) and PET2 remained independent predictors. A dismal 8-yrs EFS characterized pts with sFLC(κ+λ) above threshold (20% vs 89%; Χ2 119, p<.0001). Pts with sFLC(κ+λ) below cutoff and a negative PET2 had an EFS of 93% as compared to 36% of those with sFLC(κ+λ) above cutoff or a positive PET2. Pts with sFLC(κ+λ) above cutoff and positive PET2, had the worse outcome with an EFS <10% and a median survival <12 mo.s (Χ2 65.4; p<.0001). sFLC assay was even more valuable in identifying poor risk pts within the early unfavorable category (5-yrs EFS <25%, Χ2 51 p<.0001). By immunoistochemistry small B cells and plasmacytoid lymphocytes were identified as the main source of sFLC in HL tissues while a strong sFLC uptake by mast cells was documented. Conclusions: A cumulative amount of sFLC ≥57.1 mg/mL, is the strongest independent predictor of failure in cHL. Combining sFLC(κ+λ) and PET2 outcomes can timely discriminate poor risk pts subsets, who may benefit from upfront treatment escalation or early salvage. Our data also support that sFLC might endorse immunobiologic activities relevant to cHL pathobiology.
A prospective study investigating the impact of definitive chemoradiation in locoregionally advanced squamous cell carcinoma of the skin.
Authors: Nottage Michelle K. , Francesconi Alessandra Bastian , Houston Kathleen Emilie Mary , Lin Charles , Kenny Lizbeth M. , Hughes Brett Gordon Maxwell
Published: March 2020

8538

Background: Our state, Queensland, Australia, has the highest rate of cutaneous squamous cell cancer (SCC) in the world. Spread to regional lymph nodes or more distant sites occurs in 5-10%. A proportion of patients can not undergo surgical resection but complete response rates with radiotherapy alone are low. This led to the hypothesis that combined chemoradiation (CRT) may be of benefit. We decided to document the outcomes of concurrent chemoradiation by means of a prospective trial. Methods: This was a single arm, phase II study with planned sample size 30 patients. The primary endpoint was complete response rate (CRR), estimate 60%. Patients with locally/regionally advanced (non-metastatic) cutaneous SCC deemed unresectable or unsuitable for surgery by consensus of the multidisciplinary Head and Neck Cancer Clinic, with measurable disease, aged over 18, performance status 0-2, received definitive radiotherapy (XRT) (70Gy in 35#) and concurrent weekly platinum based chemotherapy (CT) (cisplatin 40mg/m2 or carboplatin AUC 2). Results: 14 patients were enrolled (Feb 2008-June 2011), median age 66 (48-84), 64% ECOG PS 0, 64% stage IV, 57% nodal disease only. Cisplatin/carboplatin was administered in 64%/36% respectively. 42% received all planned CT while 58% had 1 or 2 weeks omitted. 2 patients had dose reductions. XRT was completed as planned in 93%. The CRR was 57% (8/14) at analysis in December 2011 (median follow-up 13.5m). 2 further patients with partial response (PR) achieved CR after undergoing salvage surgery. Six (43%) patients had a PR; 4(29%) did not receive surgery and later progressed. Median overall survival was not reached, with 3 year survival 54%. The most frequent toxicities were dermatitis, mucositis, thrombocytopenia, nausea, anaemia, dysphagia. 28% had grade 3/4 toxicity, mainly cytopenias, infection, dehydration and nausea. Conclusions: This is the only prospective series of CRT for cutaneous squamous cell cancer. A high complete response rate was documented in patients with loco-regionally advanced disease and multiple co-morbidities, with acceptable toxicity, making this a reasonable alternative for patients unable to undergo surgery.
Vemurafenib (V) in BRAF V600E metastatic melanoma (mM): Analysis of 507 patients (pts) enrolled in the French temporary authorization for use (ATU).
Authors: Lebbe Celeste , Robert Caroline , Dreno Brigitte , Thomas Luc , Grob Jean Jacques , Meyer Nicolas , Regnier-Rosencher Elodie , Saiag Philippe , Mortier Laurent , Hospital Valerie , Duval-Modeste Anne Benedicte , Dalac-Rat Sophie , Lesimple Thierry , Guillot Bernard , Leccia Marie Thérèse , Bitoun Laurence , Bobadilla Luz , Jouary Thomas
Published: March 2020

8591

Background: V, a selective BRAF inhibitor, significantly improves OS in BRAF mutated mM. ATU is an exceptional measure making available drugs that have not yet been granted a Marketing Authorisation. We provide demographic data of pts treated by V in the ATU. Methods: V 960 mg BID was given to pts with unresectable stage IIIC or IV BRAF V600E mM. Genotyping was done on the national network of molecular genetics platforms funded by the Institut National du Cancer. Data were prospectively collected. Results: From Apr 2011 to Jan 2012, 83 sites enrolled 507 pts. 80% were treated by oncodermatologists. Pts characteristics at baseline are summarized below. Safety and efficacy data are being evaluated. Conclusions: Around 2 out of 3 patients with a BRAF mutated mM were enrolled in France in the ATU highlighting a large access to BRAF genotyping and to V. Demographic data differs from literature and clinical trials for: site of primary melanoma (reverse trunk/extremity ratio) and inclusion of pts with brain metastasis or PS>2 (excluded in CT). A high number of pts had risk factors for NMSC emphasizing the importance of the communication between oncologists and dermatologists for managing V therapy. [Table: see text]
Widespread use of complementary and alternative medicine (CAM) among non-Hodgkin lymphoma (NHL) survivors.
Authors: Leal Alexis D. , Allmer Cristine , Maurer Matthew J. , Cerhan James R. , Nowakowski Grzegorz S. , Inwards David James , Macon William R , Ehlers Shawna L. , Link Brian K. , Habermann Thomas Matthew , Thompson Carrie A.
Published: March 2020

9057

Background: The incidence of CAM use among patients with cancer is higher when compared to the general population. However, there are few studies examining CAM use in NHL survivors, and limited data are available regarding beliefs in CAM. This study was conducted to examine the prevalence of CAM use in NHL, define CAM beliefs among NHL survivors, and explore differences between patients with indolent and aggressive lymphoma. Methods: Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource from 2002-2008. NHL patients who completed the 3-year post diagnosis questionnaire, which includes questions regarding CAM use and beliefs, were included in this study. Chi-squared tests and Wilcoxon rank-sum tests were used to assess the association of CAM use with prognostic and demographic factors. Results: 719 patients were included with a median age of 63 years (range 22-92). 53% were male. Overall, 636 (89%) reported ever using CAM. 78% of patients used vitamins and 54% alternative therapies (chiropractic (36%) and massage therapy (24%)). Among CAM users, 141 (22%) believe CAM can assist the body to heal, 123 (19%) believe CAM can relieve cancer symptoms, 115 (18%) believe CAM use gives a feeling of control, 106 (17%) believe CAM can boost immunity, 24 (4%) believe CAM can cure cancer, and 35 (6%) believe CAM can prevent the spread of cancer. Female gender was associated with increased overall CAM use (p<0.0001) as well as use of vitamins (p<0.0001), herbal supplements (p=0.006) and alternative therapy (p=0.0002) specifically for cancer. Older age was also associated with increased vitamin use (p=0.005) and decreased herbal supplements use (p=0.008). There was no significant difference in overall CAM use between those with follicular lymphoma grades I-II (n=195, 91%) and non-relapsed diffuse large B-cell lymphoma (n=151, 87%), although massage therapy was utilized more often by FL survivors (29% versus 18%, p=0.005). Conclusions: CAM modalities are used by the majority of NHL survivors (89%). The assessment of CAM use and education regarding potential harms is imperative for the NHL survivor.
Biomarkers of amenorrhea and ovarian function in breast cancer survivors.
Authors: Ruddy Kathryn Jean , Gelber Shari , Tamimi Rulla M. , Ginsburg Elizabeth S , Schapira Lidia , Come Steven E. , Meyer Meghan E , Winer Eric , Partridge Ann H.
Published: March 2020

9071

Background: Ovarian function after treatment of early breast cancer may affect fertility, menopausal symptoms, endocrine therapy decision-making, and subsequent health and psychosocial concerns among young survivors. We aim to improve understanding of ovarian reserve in women with a history of breast cancer by comparing anti-mullerian hormone (AMH), estradiol (E2), and follicle-stimulating hormone (FSH) levels in survivors with and without amenorrhea, a surrogate for ovarian dysfunction and menopause. Methods: As part of an ongoing prospective multi-center cohort study, women diagnosed with breast cancer at age <41 have blood and surveys collected one year after diagnosis. Women who reported that they were receiving ovarian suppression or had undergone hysterectomy or bilateral oophorectomy/ovarian ablation were excluded. Amenorrhea was defined as >6 months between blood draw and last menstrual period. AMH, E2, and FSH levels were compared between those with and without amenorrhea using a Wilcoxon rank sum test with 2-sided p-values. Results: The first 199 eligible women with blood and survey data at one year were included in this analysis. Median age was 37 years (range 22-40). Seventy-two(36%) had received chemotherapy alone, 75 (38%) had received chemotherapy followed by tamoxifen (TAM), 25 (13%) had received TAM alone, and 10 (5%) reported TAM use but did not respond to chemotherapy items. Median AMH and E2 were lower and FSH was higher in women with amenorrhea, and these differences remained significant when those on and off TAM were analyzed separately (Table). Conclusions: AMH, E2, and FSH all are promising biomarkers for amenorrhea and residual ovarian function in young breast cancer survivors. Future research will evaluate whether AMH, E2, and FSH at baseline and early in the survivorship period predict ovarian function later. [Table: see text]
Efficacy and safety of half-dose pegfilgrastim in cancer patients receiving cytotoxic chemotherapy.
Authors: Ramaekers Ryan C. , Olsen Jon , Obermiller Angela Mae , Jabbour Melhem Salim , Tharnish Mark , Schriner Megan , Hays Rita , Nelson Deborah , Benzel Heather , Hadenfeldt Rebecca , Fuller Courtney , Copur Mehmet Sitki
Published: March 2020

9110

Background: Pegfilgrastim reduces neutropenia risk in patients (pts) on cytotoxic chemotherapy. A single 6 mg dose per chemotherapy cycle commonly causes bone pain and leukocytosis. While half-dose pegfilgrastim has been shown to be safe and effective in breast cancer pts, there is no data on half-dose pegfilgrastim in general oncology pts. Methods: We evaluated the efficacy and safety of half-dose pegfilgrastim in general oncology pts on cytotoxic chemotherapy at St Francis Cancer Center. Pts who received at least one dose of 6 mg pegfilgrastim and developed NCI-CTCAE grade 2 or more bone pain and/or leukocytosis (WBC>10,000/ml) were given 3 mg dose pegfilgrastim on their following chemotherapy cycles. Pt demographics, type/number of chemotherapy regimens, efficacy, side effects and complications were evaluated. McNemar’s test, logistic regression analysis and ANOVA were used for statistical analysis. Results: Twenty-six pts (3 males, 23 females, all Caucasian) with median age 55 (range 34-86) received a total of eighty-three 3 mg doses of pegfilgrastim. Cancers treated were breast (N=16), colorectal (N=7), head and neck (N=1), non-Hodgkin lymphoma (N=1) and non-small cell lung cancer (N=1). Chemotherapy received was anthracycline (N=9), taxane (N=7), 5-FU/oxaliplatin (N=7), 5-FU/cisplatin (N=1), gemcitabine/oxaliplatin (N=1), pemetrexed/carboplatin (N=1). No neutropenia or chemotherapy dose modifications occurred on half-dose pegfilgrastim. In the 26 pts we report, bone pain occurred in 23 pts at 6 mg and 14 pts at 3 mg dose. Leukocytosis occurred in 23 pts at 6 mg and only 2 pts at 3 mg dose (McNemar’s test, P<0.01). While older age and full-dose pegfilgrastim were predictive of bone pain, more than one line of chemotherapy and half-dose pegfilgrastim were predictive of lack of leukocytosis (logistic regression analysis/ANOVA, P<0.01). Conclusions: Half-dose pegfilgrastim in general oncology pts receiving cytotoxic chemotherapy seems to be safe and effective with less bone pain and leukocytosis without resultant neutropenia or need for chemo modification. Larger prospective studies of half-dose pegfilgrastim in this setting are needed to further understand the feasibility of this approach.
Continued suppression of bone turnover following a single dose of zoledronic acid: Time to re-think dosing intervals in the management of bone metastases?
Authors: Simmons Christine E. , Goodwin Pamela Jean , Hogeveen Sophie , Clemons Mark , Haq Rashida , Brezden Christine B. , Ebrahim Jalal , Han Dolly
Published: March 2020

9111

Background: The management of patients (pts) with bone metastases has changed significantly over the past decade, with the advent of newer, more potent anti-osteoclastic agents. However, the dosing interval in which these agents are given has not changed; pts are still dosed at a frequency of monthly or q3weekly injections. It is not known if this is the optimal dosing frequency or due to convention. The purpose of this study was to determine the duration of suppression of bone turnover by Zoledronic Acid (ZA) in a population of bisphosphonate naive metastatic breast cancer (MBC) pts. Methods: This prospective single arm phase II study enrolled 26 pts with MBC to bone who had not received bisphosphonates in the metastatic setting. A single dose of ZA was given at week 0, and biomarkers of bone turnover (serum CTX) were collected every 2 weeks subsequently. Pain scores and quality of life data were collected every 4 weeks. Pts remained on study if their biomarkers remained suppressed, but came off study as soon as escape from suppression was noted, (defined as a rise > 50% of baseline value). Results: At 12 weeks, 73% (95% CI 56%-90%) of pts had continued suppression of bone turnover demonstrated by serum CTX. The pts that escaped suppression did so at a median of 8 weeks after first infusion of ZA (range 8-10 weeks). The magnitude of suppression (proportion decrease from baseline) of serum CTX at week 4 was significantly greater in those who had continued suppression compared to those who escaped suppression before 12 weeks (75% vs 58%, p = 0.02). The absolute baseline value of CTX was significantly lower in pts who maintained suppression (507 vs. 745 ng/L, p = 0.04). Quality of life scores and pain medication use did not change appreciably during this period. Conclusions: This study suggests that ZA may not need to be given at conventional intervals in the majority of pts, and may safely be withheld without increased risk to morbidity or decline in quality of life over a 12 week period. Baseline CTX and the magnitude of suppression of bone turnover at 4 weeks may predict for the optimal dosing frequency. Confirmation in a randomized trial is needed.