bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency of carcinoma not otherwise specified (NOS) as a histologic diagnosis among non-small cell lung cancer (NSCLC) cases between 1989 to 2006: An epidemiologic study from the California Cancer Registry
Authors: Ou S. I. , Zell J. A.
Published: August 2020

e19049

Background: Recent clinical trials demonstrated differential survival benefit from different chemotherapy regimens according to NSCLC histologies. We investigated the distribution of carcinoma NOS (not otherwise specified) among NSCLC cases in California. Methods: Retrospective population-based analysis of 175,298 NSCLC patients diagnosed histologically or cytologically from the statewide California Cancer Registry from 1989 to 2006. Results: Carcinoma NOS accounted for 22.2% of all NSCLC patients, was most commonly diagnosed cytologically (36.7%) and had the worst 5-year survival estimates (5.8%) and median OS (5 months) compared to other major histologies. The proportion of carcinoma NOS was highest among stage 4 disease and increased significantly from 1989 to 2006 among all patients, both males and females, all 4 major ethnicities (Caucasian, African-American, Hispanic, and Asian), all age- categories, and all AJCC stages. The percentage of the very elderly (80+) increased from 10.8% to 17.1% among all NSCLC patients and they had the highest percentages of carcinoma NOS and cytologically-diagnosed NSCLC among all age categories. Among stage 4 patients, carcinoma NOS patients derived less survival benefit from chemotherapy than adenocarcinoma patients during the most recent period of diagnosis and Cox proportional hazards analysis indicated carcinoma NOS (vs. adenocarcinoma; HR = 1.061, 95% CI: 1.040- 1.083) and cytologically-diagnosed NSCLC (vs. histologically-diagnosed NSCLC, HR = 1.043, 95% CI: 1.024–1.062) were independent unfavorable prognostic factors for OS. Conclusions: Carcinoma NOS was a common histologic diagnosis and was increasing in proportion among NSCLC in California from 1989 to 2006. This may be partially attributed to the increasing number of the very elderly patients and stage 4 patients.

No significant financial relationships to disclose.
Evaluation of the accuracy of FDG-/FLT-PET for early prediction of non-progression in patients with advanced non-small cell lung cancer (NSCLC) treated with erlotinib
Authors: Zander T. , Scheffler M. , Nogova L. , Hellmich M. , Stoelben E. , Engel-Riedel W. , Krug B. , Dietlein M. , Neumaier B. , Wolf J.
Published: August 2020

e19054

Background: EGFR mutations predict response to erlotinib treatment in advanced NSCLC. However, also a subgroup of patients with wildtype EGFR benefits from erlotinib treatment. This subgroup could not yet be defined by molecular means. In this trial we set out to prospectively evaluate the accuracy of [18F]FDG-/[18F]FLT-PET analyses for early prediction of non-progression in chemo-naive patients with advanced NSCLC treated with erlotinib. Methods: Patients with NSCLC stage IIIB/IV without prior systemic treatment for NSCLC were eligible and treated for 6 weeks with erlotinib in this single centre diagnostic pilot trial. Primary endpoint was the accuracy of [18F]FDG/18F[FLT] PET after 1 week of treatment to predict non-progression as defined by RECIST criteria in CT scans after 6 weeks of treatment. Here we present the evaluation of 20 patients of this ongoing trial in accordance with the data monitoring board (EudraCT number 2005–005393–73; NCT00568841 ). Results: Twenty patients were recruited from 9/07 to 9/08. Seventeen patients were eligible for final analysis. The AUC for [18F]FDG PET at week 1 to predict non-progression was 0.857 ±0.105 (p=0.013) and 0.643±0.137 (p=0.32) for [18F]FLT PET. Using [18F]FDG PET specificity was 1 and sensitivity 0.71 for prediction of non- progression after six weeks (p=0.006 Fishers exact). In addition, [18F]FDG PET after 1 week of treatment clearly predicted tumor non- progression after 18 weeks of treatment with a predefined cut-off of -20% change in sSUVmax. (p=0.0004, Fisher´s exact). Finally, using this cut-off value [18F]FDG-PET after one week of treatment, predicted progression free survival (p=0.001, log rank test), with differences in median PFS of 45 days vs 320 days. Using univariable Cox regression, both [18F]FDG and [18F]FLT PET predicted PFS [hazard ratio 2.1 (p=0.006, Wald test) and 2.3 (p=0.011), respectively, per standard deviation]. Conclusions: Our observations indicate that early [18F]FDG but not [18F]FLT PET analysis predicts non-progression after 6 weeks of first-line erlotinib treatment in patients with advanced NSCLC. In addition, early [18F]FDG PET predicts non-progression after 18 weeks of treatment and progression free survival.

[Table: see text]
Treatment and outcome of patients with brain metastases from non-small cell lung cancer (NSCLC)
Authors: Ali A. , Goffin J. R. , Arnold A. , Ellis P. M.
Published: August 2020

e19058

Background: The prognosis of patients with brain metastases from NSCLC is generally poor. However, some reports suggest that the outlook of patients with brain metastases at the time of diagnosis may be similar to that of patients with advanced NSCLC without brain metastases. We undertook a retrospective review of NSCLC patients with brain metastases to examine the outcomes of care for patients with brain metastases from NSCLC. Methods: All new lung cancer patients seen in our institution between July 2005 and June 2007 were assessed for the development of brain metastases. Baseline characteristics, treatment and outcome data were extracted from the chart. The primary outcome of interest was a comparison of survival of patients with brain metastases at diagnosis compared with patients who developed brain metastases later. Results: 91 of 878 (10.4%) new patients seen over the 2 years developed brain metastases. There were 43 men and 48 women. The median age was 64 yrs (sd 10.6yrs). 45 patients had brain metastases at presentation while 46 developed brain metastases later. 34 (37%) had a solitary brain metastasis. 18 (20%) underwent surgical resection. The median overall survival for all patients was 7.8m. Patients with brain metastases at diagnosis had a significantly shorter overall survival than patients who developed brain metastases later (9.8m v 4.3m, p=0.001). Survival following diagnosis of brain metastases was similar for both groups (3.7m v 4.8m, p=0.53). Patients presenting with brain metastases were less likely to be referred to a medical oncologist (51% v 74%, p=0.02) and less likely to receive chemotherapy (18% v 41%, p=0.01). Conclusions: These data suggest that NSCLC patients with brain metastases at diagnosis have a significantly worse outcome than patients who develop brain metastases at a subsequent time point in their illness. Few patients received systemic therapy following diagnosis of brain metastases and further research is needed to determine the utility of chemotherapy in this patient group.

No significant financial relationships to disclose.
Cross-talking between bone marrow-derived cells and lung cancer cells
Authors: Zhang J. , Liao M. , Niu X. , Xiang J. , Zhao Y. , Chen H. , Lu S.
Published: August 2020

e19068

Background: Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells(BMDC, also called bone stromal cells in some publication) on lung cancer cells is largely unexplored. This study is to explore the effect from bone marrow derived cells on biological behavior of lung cancer cells. Methods: The difference among lung cancer cell lines in their abilities to bone metastasis was tested using SCID animal model. Supernatant of bone marrow aspiration(BM) and condition medium from human bone stromal cells(BSC) were used to study the activity of bone stromal factors. Affymetrix gene chip U133A 2.0 was used to study the gene expression profile of H460 cells, after exposure to secreted proteins from bone stromal cells. Results: In accordance with other literature repors, H460 was found with high bone metastasis potential, while SPC-A1 and A549 cells were low bone metastasis lung cancer cells. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to bone stromal cells consistently up-regulated 31 genes. Ontoexpress software showed main function of 31 genes were associated with signal transduction pathways(5 genes), and adhesion molecule(5 genes), including integrin b3 and ADAMTS-1, two potential targets related with bone metastasis. Conclusions: We concluded bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

No significant financial relationships to disclose.
Gefitinib versus platinum contained doublet chemotherapy in chemotherapy-naive patients with stage IIIb or IV non-small cell lung cancer of adenocarcinoma histology: A retrospective case control study
Authors: Xu Y. , Zhou Y. , Huang M. , Zou B. , Zhang X. , Zhang X. , Zhou L. , Zhu J. , Gong Y. , Hou M. , Lu Y.
Published: August 2020

e19070

Background: The results of the ISEL study in non-small cell lung cancer (NSCLC) suggest greater benefit of gefitinib among Asian patients and non-smokers compared with the overall trial population. Methods: We conducted a retrospective case-control study to compare outcomes for gefitinib versus platinum doublet chemotherapy as first line treatment in selected NSCLC patients (stage IIIB/IV adenocarcinoma, PS 0–2). Patient receiving platinum chemotherapy were selected on the basis of disease stage (IIIB or IV), gender, smoking history, WHO performance status (PS) (0–1, or 2) and age (< 60ys or ≥ 60ys) being matched to patients receiving gefitinib. Gefitinib and chemotherapy arm patients were selected by 1:2 ratio in order to increase statistical power. The study was approved by local institute review board. Results: 99 chemo-naïve adenocarcinoma patients treated in our institute from January 2006 to December 2007 were collected: 33 received gefitinib and 66 received chemotherapy. The baseline characteristics are listed in table 1 . The median duration of follow-up was 10 months. Patients receiving gefitinib experienced significantly higher ORR and DCR, and prolonged PFS ( table 1 ). Patients receiving chemotherapy experienced more frequent grade 3–4 neutropenia (42.4% vs 0%), thrombocytopenia (21.2% Vs 0%), febrile neutropenia (7.5% vs 0%) and nausea (24.2% vs 3.0%). The most commonly recorded adverse events in the gefitinib arm were rash/acne (9.1%), diarrhea (3.0%), nausea (3.0%) and anemia (3.0%). Conclusions: The limitations of case-control studies are acknowledged, yet these results were supported by IPASS. Gefitinib as first-line treatment confers clinically relevant benefit in Asian NSCLC patients with adenocarcinoma histology versus platinum based chemotherapy.

[Table: see text]

[Table: see text]
KRAS mutation in the primary or acquired resistance of Chinese NSCLC to EGFR tyrosine kinase inhibitors
Authors: Chen H. , Wu Y. , Zhang X. , Chen Z. , Guo A. , Cheng H.
Published: August 2020

e19071

Background: Prevalence of KRAS mutation in Asian NSCLC is different to population of white ethnicity. Data about KRAS mutation after development of resistance to EGFR tyrosine kinase inhibitors (TKIs) are rare. This study was to investigate the prevalence of KRAS mutation in Chinese NSCLC after primary or acquired resistance to EGFR TKIs. Methods: 155 EGFR TKI-naive NSCLC patients and corresponding tumor specimens were collected to establish baseline of KRAS mutation. 45 specimens from six patients with primary resistance to TKIs and twenty-nine patients with acquired resistance to TKIs were analyzed. Genomic DNA was prepared after purified cancer cells were isolated by laser microdissection. Mutations in codon 12 and 13 of the KRAS gene in TKI-naive patients were analyzed by direct sequencing. Mutations in TKI-resistant patients were meanwhile detected by DxS KRAS Mutation Test Kit and direct sequencing. Results: KRAS mutation (G12X) was detected in 7.1% (11/155) of the TKI- naive patients by direct sequencing. In 6 primary resistant patients (two paired specimens and four resistant specimens) and in 29 acquired resistant patients (eight paired specimens and twenty-one resistant specimens), absence of KRAS mutation was detected in all pre- treatment and post-treatment tissues by both methods. Conclusions: KRAS mutation exists in TKI-naive NSCLC patients instead of TKI-resistant setting. KRAS mutation couldn’t thoroughly explain the primary resistance to EGFR TKIs and it might not be the crucial consideration in the mechanisms of acquired resistance.

No significant financial relationships to disclose.
Microarray study of gene expression profiles in peripheral blood samples from lung cancer patients before and after erlotinib treatment
Authors: Irigoyen A. , Olmedo C. , Valdivia J. , Comino A. , Cano C. , Luque R. , Conde V. , Delgado J. , Blanco A. , Bueno P.
Published: August 2020

e19072

Background: The gene expression profile in peripheral blood samples from lung cancer patients is a potential predictor to treatment response. Methods: The study has been developed using 10 healthy volunteers as the control group and 10 lung cancer patients (stage IV). Written informed consent was obtained being the protocol approved by the local Clinical Research and Ethics Committee. Peripheral blood samples were obtained from lung cancer patients before (T0) and after treatment (T15d). RNA from peripheral blood samples was extracted and purified selecting 28S/18S ratios>1.5 to obtain cDNA and cRNA for hybridization of the 20,000 genes included in Human 20K CodeLink. An array from each participant was obtained in duplicate. For each array, 2 μg of cRNA was compared to 2 μg of healthy cRNA.. Significant genes were found using Significance Analysis of Microarrays which uses repeated permutations of the data. Results: The selected genes were expressed >3-fold with a false discovery rate =0.05. Before treatment (T0) when patients were compared to healthy volunteers there was an increase in the expression of: histone 1 H4c, transforming growth factor beta 2, endothelial cell growth factor 1 (platelet-derived), glucose-6-phosphatase catalytic 2, Relaxin 3 receptor 1, Insulin-like growth factor binding protein 2, RAS-like family 11 member B, and ELK4. After treatment (T15d), when each lung cancer patient's results were compared to their own before treatment results (T0), there was an increase in the expression of: Bcl2, myosin light polypeptide 4; interferon alpha-inducible protein 27; interferon gamma receptor 1; RASSF5, ARHGEF6, IGFBP5, tumor protein p53 inducible nuclear protein 1, peroxisome proliferative activated receptor gamma. Conclusions: The data presented identifies biologically relevant over-expressed genes in lung cancer. A validation of these results and the analysis of the genes that identify patients who will respond positively to erlotinib treatment is being carried out.

No significant financial relationships to disclose.
Safety and effectiveness of malignant pleural mesothelioma patients treated with pemetrexed: A postmarketing drug registered study under performance linked access system
Authors: Watanabe M. , Yamamoto T. , Arakawa K. , Imai J. , Sekiguchi R. , Enatsu S. , Nambu Y.
Published: August 2020

e19084

Background: Approximately 1000 patients are newly diagnosed as malignant pleural mesothelioma (MPM) each year in Japan, however MPM patient profile and their outcome are not well understood. Pemetrexed is the only approved chemotherapeutic agent for MPM. Limited safety information was available at launch of pemetrexed in Japan where drug induced interstitial pneumonitis are reported at higher rate than the rest of the world. Therefore postmarketing drug registered study (PDRS) for pemetrexed was conducted in Japan to investigate patient characteristics, adverse events and survival of MPM patients based on a regulatory requirement for approval. Methods: From February 2007 to May 2008, all of histologically proven MPM patients to be treated with pemetrexed were required to register the PDRS in Japan. The observation period was six-months. Supply of pemetrexed was restricted to institutes with experienced medical oncologists based on pre-determined criteria. Results: During the 15-months enrollment period, 948 MPM patients were registered. Until August 3th 2008, data for 437 patients were collected. Among these, 389 were male, 48 female, median of age 65 (35–86). 72.3% patients had a known history of being exposed to asbestos. The treatment regimen mainly consists of 500 mg/m2 of pemetrexed and 75 mg/m2 of cisplatin every 21 days. Median treatment cycle was 3.0. Hematological NCI-CTC Grade ¾ adverse events in laboratory data were hemoglobin decrease 19.9 %, neutropenia 20.1%, thrombocytopenia 7.6%. Serious non-hematological adverse events were nausea 3%, vomiting 3.2%, fatigue 0.2%, constipation 0.2%, diarrhea 0.9%. Pneumotoxicity was found in 1.4%. 152 deaths (34.8%) were observed and six-month survival rate estimated by Kaplan-Meier method was 70.9%. Conclusions: This large size PDRS shows that safety profile of pemetrexed appeared similar to the previous clinical trial without additional safety signal. The study has minimum selection bias and provides useful information to health care professionals on safety and effectiveness of pemetrexed in real clinical setting in Japan.

[Table: see text]
Is hepcidin involved in anemia of advanced non-small cell lung carcinoma (NSCLC) patients treated with platin-based chemotherapy? An exploratory study
Authors: De Castro J. , Cejas P. , Belda-Iniesta C. , Ramirez-Merino N. , Barriuso J. , Hernandez-Agudo E. , Feliu J. , Moreno-Garcia V. , Martinez-Marin V. , Gonzalez-Baron M.
Published: August 2020

e19086

Background: Anemia is a common complication in NSCLC patients. Hepcidin, a liver-produced peptide, acts to cause a block on cellular iron export by internalisation and degradation of ferroportin.This results in iron sequestration and interrupts iron delivery to erythroid precursor cells thus causing anemia. To date there are no studies addressing whether hepcidin expression contributes to the anemia in NSCLC. Methods: to investigate whether hepcidin is implicated in NSCLC anemia, hemoglobin (Hb), iron metabolism and serum hepcidin levels, were studied in newly diagnosed advanced NSCLC patients. Blood samples of each patients were collected before starting cisplatin based chemotherapy treatment. Serum was separate by centrifugation at 2,500 g for 10 min at 4ºC. Hepcidin was detected by a solid phase enzyme-linked immunosorbent assay (ELISA) on the serum of each patient. The ELISA test is based on the principle of competitive binding. The microtiter wells are coated with a polyclonal antibody directed towards an antigenic site on the hepcidin prohormone molecule. Endogenous hepcidin prohormone of patient sample competes with a hepcidin prohormone biotin conjugate for binding to the coated antibody. Hepcidin absolute quantitation was achieved using a standard curve. Hepcidin results were correlated with serum parameters related to iron metabolism. Results: In a exploratory analysis, 20 patients with advanced NSCLC were selected for hepcidin prohormone detection. Only 10% were anemic at the diagnosis but 70% developped anemia during the treatment. 50% of the patients had iron deficiency. 70% received treatment for anemia (40% erythropoetin and iron, 20% iron, 10% erythropoetin). Median serum hepcidin levels was 151 ng/ml (range 99–308). The serum hepcidin level correlated with serum ferritin but no correlation was found with other iron metabolism parameters. An inverse correlation was seen between serum hepcidin level and Hb evolution after 4 cycles of chemotherapy. Conclusions: These results support a potential relationship between hepcidin expression and anemia in NSCLC patients. Further confirmatory study is ongoing and final results will be presented in the meeting.

No significant financial relationships to disclose.
A phase II study of docetaxel and carboplatin in patients with advanced non-small cell lung cancer after treatment with non-platinum regimens
Authors: Ikeda T. , Fukuda M. , Fukuda M. , Soejima Y. , Doi S. , Nagashima S. , Nakamura Y. , Soda H. , Oka M. , Kohno S.
Published: August 2020

e19087

Background: Docetaxel and platinum is active in patients with non-small cell lung cancer (NSCLC) as first-line chemotherapy, and docetaxel is also effective in previously-treated patients. This study was designed to evaluate activity and toxicity of docetaxel and carboplatin as second-line chemotherapy in advanced NSCLC patients treated with non-platinum regimens. Methods: Patients with stage IIIB or IV NSCLC treated with non-platinum regimens, a performance status ≤ 2, and an adequate organ function were eligible. Patients were treated with docetaxel 50 mg/m2/day and carboplatin AUC 5 mg/ml/min on day 1 of each 21-day cycle. Primary endpoint was response rate. Results: Twenty-nine patients with a median age of 63 years were included. Median number of cycles for docetaxel and carboplatin was 3.2. Grade 3/4 neutropenia and anemia occurred in 21 (72.4%) and 2 patients (7.0%), respectively. Febrile neutropenia occurred in 2 patients (7.0%). Grade 3 non-hematological toxicity included diarrhea and peripheral neuropathy in each 1 patients (3.5%). Complete and partial response was observed in 1 and 4 patients, respectively. Overall response rate was 17.2% (95%CI: 5.9–35.8). Median survival time was 12.7 months (95%CI: 7.8–17.6) and 1- year survival rate was 52.5% (95%CI: 31.8–73.2). Conclusions: The combination of docetaxel and carboplatin as second-line chemotherapy may be promising in advanced NSCLC patients treated with non-platinum regimens.

No significant financial relationships to disclose.
Bevacizumab (B), cisplatin, and vinorelbine in chemotherapy-naive patients (p) with nonsquamous non-small cell lung cancer (NSCLC): A Galician Lung Cancer Group phase II study
Authors: Leon L. , Vázquez S. , Gracia J. M. , Lázaro M. , Fírvida J. L. , Casal J. , Amenedo M. , Santomé L. , Gallego R. , Anido U.
Published: August 2020

e19089

Background: Bevacizumab, an anti-VEGF monoclonal antibody, improves response rates and prolongs survival in p with non squamous NSCLC when combined with carboplatin-paclitaxel or cisplatin-gemcitabine. This single-arm, open-labeled phase II trial aims to evaluate the efficacy and safety profile of B in combination with another widely used chemotherapy doublet for NSCLC: cisplatin and vinorelbine. Methods: Chemotherapy-naïve p diagnosed with stage IIIB or IV non squamous NSCLC received cisplatin (80 mg/m2), vinorelbine (25 mg/m2 IV days 1 and 8) and B (15 mg/kg IV) on day 1 every 3 weeks for up to 6 cycles followed by B 15 mg/kg alone every 3 weeks until disease progression. Main eligibility criteria were: PS 0–1, no brain metastases, no history of hemoptysis, stable cardiac condition and no full dose anticoagulation. Primary endpoint was progression-free survival and secondary endpoints were RR, duration of response, OS, 1-year survival and safety profile of the combination. Results: 38 p have been enrolled in the study and data of 27 p have been included in this analysis. P characteristics were: male 66.7%; median age 57 years (range 41–74); ECOG PS 0/1 (%) 33.3/66.7; adenocarcinoma/other (%) 74.1/25.9; stage IIIB/IV (%) 25.9/74.1. Median number of cycles for B/cisplatin/vinorelbine was 4.0 (range 1–6) and median number of cycles for B maintenance was 2 (range 1–4). 17 p were evaluable for response according to RECIST criteria: PR 29.4% and SD 41.2%. With a median follow-up of 3.9 months (range 0.7–11.1), median PFS was 4.6 months (95% CI: 2.6–6.6) and median OS has not been reached yet. Hematological toxicities were: 1 p gr. 3 anemia; 2 p gr. 3 and 2 p gr. 4 leucopenia; 10 p gr. 3, 1 p gr. 4 neutropenia and 3 p febrile neutropenia. Most common grade 3/4 non hematological toxicities were: vomiting (1p gr. 4), high blood pressure, asthenia and hyperglycemia. 1 p experienced gr. 4 abdominal pain, 1 p. gr. 4 constipation, 1 p. gr. 4 nausea and 1 p gr. 4 respiratory infection. No grade 3/4 hemoptysis were reported. Conclusions: This interim analysis shows that B in combination with cisplatin and vinorelbine is safe and well tolerated and has a promising activity in chemo-naïve p with non squamous NSCLC. Survival data will be updated.

[Table: see text]
Randomized phase III trials of standard chemotherapy with or without targeted agents as first-line therapy in non-small cell lung cancer
Authors: Hoang T.
Published: August 2020

e19092

Purpose: To characterize the pattern and outcome of randomized phase III trials involving standard chemotherapy with/without novel agents as first-line treatment in advanced NSCLC patients (pts). Methods: The trials included in this analysis were identified through a search of MEDLINE as well as websites (ASCO, IASLC) and meeting proceedings. Studies comparing novel agents alone to standard regimens were excluded. Results: Of 20 identified trials (16,050 pts), 11 (8,647 pts) were published between 2004–2008, and 9 (7,403 pts) were reported at scientific meetings (mostly between 2005–2008), but have not been published yet. All studies were conducted within the last 10 years. Majority were industry-sponsored studies; 4 (20%) were conducted by cooperative or non-profit groups. Chemotherapy chosen as the standard regimens involved cisplatin or carboplatin in combination with a third-generation drug with paclitaxel (10 trials) and gemcitabine (6 trials) being the most common drugs. The experimental drugs included agents with different molecular targets (EGFR, VEGF, MMP, PKC, FTI, TLR-9¼). Overall survival was primary endpoint in all 11 published studies. PFS was chosen as primary in 2 non-published studies. When comparing the standard arms (chemotherapy alone) across the 11 published trials, there was a large difference in term of response rate RR (15% to 47%), while survival endpoints showed a smaller difference (median overall survival OS 9–10.9 months; progression free survival PFS 4.5–5.5 months; and time to progression TTP 4.9–6 months). Among 11 published studies, only one showed positive result with a consistency in all endpoints (OS, PFS and RR). Of 9 non-published studies, 2 studies were reported as positive by the investigators, although preliminary results of primary and secondary endpoints were somewhat inconsistent. Conclusions: Within the last decade, 20 randomized phase III trials involving a large number of chemo-naïve NSCLC patients were conducted. There was a variation in eligibility and patient characteristics, study design (primary endpoints) as well as results among the studies.

No significant financial relationships to disclose.
Treatment guided by ERCC1, RRM1, and BRCA1 protein expression in patients with advanced-stage NSCLC
Authors: Han B. , Shen J. , Gao Z.
Published: August 2020

e19094

Purpose: We investigated whether Treatment Guided by ERCC1,RRM1 and BRCA1 protein expression levels could improve clinical outcomes in Patients With Advanced-Stage NSCLC. Experimental Design: Eligibility: Main inclusion criteria: Stage IV or stage IIIB NSCLC; Eastern Cooperative Oncology Group(ECOG) performance status (PS) 0–1; Measurable disease; Adequate bone marrow, kidney, liver function. Main exclusion criteria: previous NSCLC therapy; Central nervous system metastasis; Requiring immediate intervention or Untreated with radiation within 28 days of study regimen initiation. Previously untreated patients with Stage IV or stage IIIB NSCLC(N=180): Standard chemotherapy group(N=60): Cisplatin 75mg/m2 Day1+Vinorelbine 25mg/m2 Days 1,8 every 28 days; Individualized chemotherapy group (N=120) (ERCC1,RRM1 and BRCA1 protein expression assayed with IHC); Low ERCC1 protein expression subgroup: Cisplatin 75mg/m2 Day1+Vinorelbine 25mg/m2 Days 1,8 every 28 days; High ERCC1 protein subgroup: Vinorelbine 25mg/m2 Days 1,8+Gemcitabine 1250mg/m2 Days 1,8 every 28 days. Description of Current Analysis: ERCC1,RRM1 and BRCA1 protein expression assayed with IHC; Assigned treatment based on ERCC1 protein expression; Primary endpoint: overall response rate; Secondary endpoints: Overall survival (OS), Progression-free survival (PFS). Enrollment progress (As of time Dec-31–2008): See Table .

[Table: see text]

No significant financial relationships to disclose.
Effect of zoledronic acid combined with cisplatin and paclitaxel on inhibition of non-small cell lung cancer cell lines
Authors: Gao Z. , Han B. , Teng J.
Published: August 2020

e19095

Backgrounds: Recent studies reported that zoledronic acid, a biphosphonate with proposed apoptotic activity, could cause a direct antitumor effect. Our prior study [J Clin Oncol 26: 2008 (May 20 suppl; abstr 19116)] reported that Zoledronic acid combined with Cisplatin shows significantly synergistic antitumor effects on lung cancer cell line A549 and subcutaneous implanted tumor on nude mice. Investigate whether zoledronic acid, augmented the cytotoxicity of cisplatin and/or paclitaxel in A549 lung cancer cell line. Methods: This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Flow cytometry was used to examine cell cycle,cell apoptosis rate. Results: Zoledronic acid in in 50 micromolar (mM) concentration augmented the cytotoxicity by cisplatin in 10μmol/L and paclitaxel in 5μmol/L. Zoledronic acid could inhibit the proliferation of lung cancer cells in vitro,which was associated with arresting of G1 phase and inducing apoptosis by a time-dependent and dose-dependentmanner. The apoptosis rate of cell increased after zoledronic acid combined with cisplatin and/or paclitaxel. Conclusions: Zoledronic acid can induce apoptosis and block cell cycle of lung cancer cells. Zoledronic acid has also shown synergistic antitumor effects when combined with cisplatin and/or paclitaxel. The clinical potential of this finding should be further studied.

No significant financial relationships to disclose.
Cisplatin (CDDP) plus oral vinorelbine (NVBO) as first-line treatment for advanced non-small cell lung cancer (NSCLC): Prospective analysis to improve the patient's convenience on day 8 NVBO administration
Authors: Sanchez A. , Provencio M. , Artal A. , Constenla M. , Garcia-Gomez R. , Viñolas N. , Domine M. , Perez F. J. , Gayo J.
Published: August 2020

e19096

Background: Severe neutropenia observed during chemotherapy (CT) is a clinical finding leading to treatment modification and, sometimes, life-threatening events. The results of a previous study with 180 p treated with IV vinorelbine plus CDDP as first-line treatment for advanced NSCLC could lead to consider not performing a blood count prior to day 8 vinorelbine administration for patients aged 70 years (y) or less who presented a good haematological tolerability profile during previous cycles (cy) in order to improve treatment convenience. The aim of this study is to prospectively validate these results with the combination of NVBO plus CDDP. Methods: Between October 2007 and September 2008, 31 chemo-naïve p with histologically confirmed stage IIIB/IV NSCLC were included. Treatment consisted of CDDP 75 mg/m2 day 1 plus NVBO 80 mg/m2 days 1 and 8, with a prior test of myelosensitivity at 60 mg/m2 for the first cycle, every 21 days. Patient's characteristics were: Median age, 62 years (range 32–73); males, 93.5%; smokers, 38.7%; all PS 0–1; adenocarcinoma, 33.3% / squamous, 36.7%; stage IIIB, 14.8% / IV, 85.2%. Results: We analyzed 129 cy. NVBO administration on day 8 was cancelled in 3 cycles due to haematological events (2.3% [95% CI: 0.4%-6.6%]. The reported events were: 1 grade-2 neutropenia, 1 grade-4 neutropenia and 1 grade- 2 thrombocytopenia. Among 22 p evaluable for response, 10 p achieved partial response (overall response rate, 45.5% [95% CI: 24.4- 67.8]). Toxicity was mild with neutropenia WHO grade 3–4 observed in 2.1% cy (9.7% p), leukopenia grade 3 in 1.4% cy (6.5% p); 1 case of febrile neutropenia was reported. Grade-3 fatigue was observed in 6 cy (6 p), grade-3 nausea in 2 cy (2 p) and grade-3 vomiting in 2 cy (2 p). Conclusions: The findings of this study could lead to consider not performing a blood count prior to day 8 NVBO administration for patients aged 70 y or less who presented a good haematological tolerability profile during previous cycles in first-line treatment for advanced NSCLC.

[Table: see text]
Use of gemcitabine plus vinorelbine (GV) to treat advanced and metastatic non-small cell lung cancer (NSCLC) in second line after recurrent disease
Authors: Gamaz M. B. , Bouzid K.
Published: August 2020

e19104

Background: Docetaxel is approved as second-line monotherapy in advanced NSCLC. In this study, we evaluate the efficacy, safety and survival of gemcitabine + vinorelbine in patients with advanced NSCLC previously treated with platine salts + taxane. Methods: From January 2007 to October 2008, twenty three patients with NSCLC stage IIIB or IV who received platine salts + taxane in first line were treated in second line with (GV) gemcitabine (G) 1,250 mg/m2 D1 and D8 + vinorelbine (V) 25 mg/m2 D1 and D8 every three weeks. Twenty one male and 2 female, median age was 59.3 (range 40 -71) years. Twelve (12) patients had IIIB stage and 11 patients had IV stage disease. Squamous cell cancer was found in 12 patients, adenocarcinoma in 11 patients. Results: No objective response were observed, stable disease was achieved in 7 (30.4 %) patients, and disease progression was observed in 16 (69.5 %) patients. Toxicities grade ¾ was 15 %, mainly hematological (leucopenia and anemia). Median follow up was 14 months, median TTP was 6 months and median survival was 7.1 months. Conclusions: Gemcitabine + Vinorelbine could be another alternative for treatment of NSCLC in second line after recurrent disease when first line chemotherapy is platine + docetaxel.

No significant financial relationships to disclose.
Current treatment (Tx) patterns in relapsed or refractory multiple myeloma (MM): A retrospective chart review study
Authors: Reece D. E. , Zaman F. , Teixeira B. L. , Yoong K. , Camacho F. , Plante R. K.
Published: August 2020

e19503

Background: New Tx options, including IMiDs [thalidomide, lenalidomide (Revlimid)] and bortezomib (Bz) (Velcade), have in the last few years become available on the market or as investigational agents in Canada for relapsed or refractory MM. These new agents are changing the Tx pattern and the clinical outcome of this disease. Methods: This retrospective chart review included all relapsed/refractory MM Pts who initiated drug Tx between Jul-06 and Jun-07 inclusive at Princess Margaret Hospital, Toronto, ON. Results: A total of 151 Pts were treated for relapsed/refractory MM between Jul-06 & Jun-07. 57 Pts (40 receiving IMiD, 14 Bz, 3 other) were on clinical trials and thus not included in the analysis due to proprietary restrictions. Mean age, % male and BSA was 64.8 (SD±9.5) yrs, 68.1%, 1.9 (SD±0.2), respectively. Time from diagnosis to current therapy was 46.3 (SD±24.7) months. Nearly half the Pts were receiving treatment for 1st disease relapse (48.9%), 24.5% for 2nd relapse, 14.9% for 3rd relapse, and the remainder for ≥ 4th relapse. 74.5% of Pts had received at least 1 stem SCT prior to current study Tx. Current Txs included cyclophosphamide ± steroid (36.2%), Bz-based (26.6%), IMiD-based [17.0% (thalidomide only)], steroid monotherapy (13.8%), melphalan + prednisone (1.1%) and other (5.3%). Overall best RR was 43.6%, and 41.5% of Pts experienced PD up to the follow-up period. Mean TTP was 9.6 (SE±0.5) months. 30.9% of Pts received ESAs, 12.8% of Pts required RBC or platelet transfusion, 6.4% of Pts received G-CSF, and 47.9% of Pts received supportive pain medication. 27.7% of Pts required unscheduled hospitalization (56.4% due to MM and 7.7% due to Tx). Incidence of any grade drug-related varicella zoster, increased neuropathic pain, and thromboembolic events were 6.4%, 16.0%, 2.1%, respectively. Four Pts died while on current Tx and 14 died during the follow-up period of up to Dec-07. Conclusions: Bz was rarely used prior to public funding in Jul-06. Since then Bz (either as monotherapy or in combination) is the most commonly used novel Tx outside a clinical study and is replacing the use of the older agents. As the first analysis of current real world MM Txs in Canada from a large tertiary academic centre, this data is reflective of emerging treatment trends.

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Evaluation of brain natriuretic peptide (BNP), troponin levels, and left ventricular ejection fraction (LVEF) in older adults with diffuse large B cell lymphoma (DLBCL)
Authors: Rodriguez M. A. , Wei W. , Huang X. , Fisch M. , Durand J. B.
Published: August 2020

e19506

Background: Troponin and BNP are markers that rise acutely during myocardial injury and cardiac dysfunction, respectively. Doxorubicin (Dox) is an effective drug for treatment of DLBCL, in the regimen RCHOP (Coiffier, et.al. NEJM, 2002). Dox has risk of myocardial toxicity, which is higher in older patients (pts). Pegylated liposomal doxorubicin (D) has greater cardiac safety yet similar efficacy to Dox in breast cancer. D replaced Dox in RCHOP (DRCOP) in a phase II study in patients >60 yrs of age, with troponin and BNP levels pre and post-treatment to see if they would predict a fall in LVEF secondary to DRCOP. Methods: DRCOP is: Rituximab 375 mg/m2 IV day (d) 1; D 40 mg/m2 IV d 1; cyclophosphamide 750 mg/m2 IV d 1; vincristine 2 mg IV d 1 total dose; prednisone 100 mg/d p.o. d 1–5. Eligibility criteria: > 60 years; untreated DLBCL; Ann Arbor stage II-IV; baseline LVEF ≥ 50%. Consult at baseline by Cardiologist required, and at follow-up as indicated. The Wilcoxon rank sign test was used to compare baseline BNP with subsequent BNP. A linear mixed model was used to assess the effect of time on troponin at baseline, midpoint and endpoint. All tests were two-sided and p-values of 0.05 or less were considered statistically significant.. Statistical analysis was carried out using SAS version 9 (SAS Institute, Cary, NC). Results: 60 patients are enrolled; only one patient has developed systolic dysfunction, (LVEF to <50%). Conclusions: DLBLC older patients Older adults with DLBCL treated with DRCOP maintain preserved LVEF and troponin levels, suggesting less cardiotoxicity. There is a significant rise in BNP without clinical cardiac dysfunction. This is a new observation that merits further study.

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No significant financial relationships to disclose.
Effect of dose on denileukin diftitox (Dd) response in treatment-naïve cutaneous T-cell lymphoma (CTCL) subjects: A retrospective analysis of three phase III studies
Authors: Dang N. H. , Sun Y. , Gao J.
Published: August 2020

e19509

Background: Three phase III studies (10, 11, 14) have been conducted with Dd, a novel IL-2 receptor-targeted recombinant fusion protein, in subjects with CTCL. Dd is approved for the treatment of persistent/recurrent CD25(+) CTCL and is the most extensively studied agent in CTCL. We retrospectively analyzed the efficacy of two Dd doses in treatment-naïve CD25(+) CTCL subjects to understand the relationship between dose and response to therapy. Methods: Studies 10 and 11 included early or advanced stage CD25(+) subjects (CD25 immunostaining in >20% of malignant cells) while 14 included CD25(-). Subjects received 9 or 18 mcg/kg/day IV for 5 days, repeating every 21 days for up to 8 courses; subjects in study 14 only received the higher dose. Study 11 included a placebo arm. Subject demographics were similar among the three studies and between the 2 dose groups in each. Response confirmation required ≥2 consecutive courses (3 observations) and was adjudicated by an independent Data Endpoint Review Committee in each study, using a weighted severity skin, blood and lymph node count. The primary endpoint was ORR (CR, CCR, PR) and the key secondary endpoint was progression-free survival (PFS). Results: Integrated efficacy results for ORR and PFS are shown in the table for treatment-naïve CD25(+) subjects. In general, the nature and incidence of the adverse events reported in the 3 studies were similar, with studies 11 and 14 proving to be broadly consistent with study 10 in terms of safety. Tolerability of 9 and 18 mcg/kg/d was similar in study 10. In study 11, the only AEs that were more frequent in the high-dose group were vomiting (13.3% vs 34.5%) and dysgeusia (0% vs 10.9%). Conclusions: Overall, there was a trend towards higher efficacy favoring 18 mcg/kg/day in treatment-naïve CD25(+) subjects. The ORR was statistically significant for the higher dose group.

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Helicobacter pylori-independent MALT lymphoma patients responsive to thalidomide—the molecular mechanism and the clinical application
Authors: Kuo S. , Chen L. , Wu M. , Hsu C. , Lin C. , Hsu P. , Yeh K. , Tzeng Y. , Cheng A.
Published: August 2020

e19512

Background: We have recently demonstrated that nuclear expression of BCL10 or NF-κB helps predict H. pylori-independent status; and inflammatory cytokines such as TNF-α may be related to BCL10 nuclear translocation (Blood 2005;106:1037–41;J Biol Chem 2006;281:167–75). Recent studies have been shown that the chimeric protein of t(11;18)(q21;q21) can lead to constitutive NF-κB activity and thereby mediate cell survival and anti-apoptotic signals. The present study was conducted to investigate the molecular mechanism and the clinical efficacy of thalidomide, an TNF-α or NF-κB inhibitor, in H. pylori-independent MALT lymphoma. Methods: Between October 2003 and June 2007, our study enrolled 11 H. pylori-independent MALT lymphoma patients ( 7 men and 4 women; age range, 43 to 79 years; 7 patients who had failed chemotherapy or rituximab) with nuclear expression of BCL10 or NF-κB in pretreatment lymphoma tissues treated at National Taiwan University Hospital with thalidomide 100mg to 200 mg oral given daily. The presence of t(11;18)(q21;q21) was identified by a multiplex reverse transcriptase polymerase chain reaction of the API2-MALT1 chimeric transcript. Results: Three (27.3%) of 11 patients achieved a complete response (CR), and 3 (27.3) of 11 patients achieved a partial response (PR), resulting in an overall response rate of 54.5% (95% CI, 19.5%-89.6%). The median time from thalidomide therapy to CR was 3.0 months (range, 2.7–4.9 months). At a median follow-up of 41.6 months (range, 17.7–63.8 months), the 3-year event-free survival and overall survival after thalidomide treatment was 80.8%, and 88.9%, respectively. The API2-MALT1 fusion transcript for t(11;18)(q21;q21) was detected in 1 (16.7%) of 6 patients with CR or PR, and 4 (80.0%) of 5 patients with stable or progressive disease (P = 0.08). Conclusions: Our results indicate that thalidomide can be an adjuvant treatment for H. pylori-independent MALT lymphoma patients. Additional investigation of the molecular mechanisms and biologic significance of the API2-MALT1 fusion transcript responsible for thalidomide resistance in this group of tumors is needed.

No significant financial relationships to disclose.
Long term follow-up of primary B and T cell non-Hodgkin's lymphoma (NHL) of the gastrointestinal (GI) tract
Authors: Cadoo K. A. , Lowery M. A. , Cumiskey J. , McCaffrey J. , Carney D. N.
Published: August 2020

e19516

Background: Anthracycline based chemotherapy is the treatment of choice for aggressive primary lymphomas of the GI tract, with surgery reserved for management of complications. We report long term follow up of 71 cases of primary GI NHL treated with chemotherapy and/or surgery. Methods: Cases were identified from the institutional histology database & records reviewed. Results: 71 patients over an 24 year period were identified; 43 (61%) male, 28 (39%) female. Median age at diagnosis was 60 (15–83). 52 (73%) were DLBCL, 11 (16%) were T-cell, 8 (11%) were MALT. The 8 patients with MALT were treated with single agent chemotherapy; 7 (88%) are alive at median follow up of 8.5 years (2–16). Of the aggressive lymphomas (63), all patients with T cell lymphoma had small bowel as primary site and histological evidence of celiac associated enteropathy, even in the absence of known celiac disease. Primary sites of DLBCL were stomach 35 (67%), small bowel 11 (21%) & colon 6 (12%). 39 (62%) patients underwent surgery at diagnosis due to acute presentation with perforation, bleeding or obstruction, or to obtain histology. Following confirmed diagnosis, 61 patients received anthracycline based chemotherapy. 2 patients with T cell lymphoma presented with perforation, were treated with surgery only and died of rapid disease progression. Of the 63 patients with aggressive NHL, 37 (59%) remain alive & disease free at median follow up of 13 years (1–24). 35 (67%) patients with DLBCL are alive & disease free. Only 2 (18%) of the T cell lymphomas are alive & disease free. 5 deaths in the DLBCL group were not related to cancer or treatment. All deaths in the T cell group were due to progressive disease. There was no difference in survival between patients treated with chemotherapy only and those who also underwent surgery. Conclusions: Patients with aggressive primary B cell GI NHL have almost 70 % survival following anthracycline based chemotherapy. However, in contrast, coeliac enteropathy associated T-cell lymphomas present with rapidly progressive disease & have a survival of < 20% with chemotherapy and/or surgery. A novel therapeutic approach is required to improve outcome in this group.

No significant financial relationships to disclose.
Diagnostic and prognostic use of FDG-PET scans in Waldenstrom's macroglobulinemia
Authors: Harris B. , Leleu X. , Leduc R. , Yarar D. , Sam A. , Rourke M. , Chuma S. , Roccaro A. , Ghobrial I.
Published: August 2020

e19518

Background: Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma. More sensitive tools of tumor burden and prognosis are needed in these patients (pts). The use of FDG-PET has not been previously studied in WM but has proved an effective diagnostic and prognostic tool effective in low-grade lymphomas. Therefore the objective of this study was to determine whether FDG-PET was an effective tool in evaluating pts with WM. Methods: We included all pts enrolled on a prospective phase II clinical trial of bortezomib and rituximab for pts with upfront or relapsed/refractory (RR) WM. All pts were CD20 positive with histologically confirmed disease and underwent staging evaluation by FDG-PET in combination with CT scan before and after therapy. Patients received 6 cycles of bortezomib IV weekly at 1.6mg/m2 on days 1, 8, 15q28 and rituximab at 375 mg/m2 on days 1, 8, 15 and 22 in cycles 1 and 4. Correlation was made with the international prognostic scoring system for WM and monoclonal protein response rate. Results: 53 pts were included, of which 35 were RR and 18 pts were upfront. Median age was 63 years (range 42–81), 64% were male. Before therapy, 34 pts (64.2%) had positive FDG-PET findings with a median IgM of 2825, Beta 2 microglobulin of 3.6, and Age of 61. 36 pts showed a minor response or greater with a correlation to negative PETs after therapy. Conclusions: Over 60% of WM pts demonstrated FDG-avid disease when using FDG-PET scans, with the majority showing negative disease after therapy. This correlates with the 67.9% response rate. Positive PET images were inversely correlated to IgM level and directly related to elevated Beta-2 microglobulin and age. Significantly PET positive individuals may demonstrate a poorer prognosis. FDG-PET scans may prove an effective tool in the diagnosis and prognosis in WM.

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