bluuebunny/crossref_metadata_2025 huggingface dataset:
Bevacizumab in combination with taxane versus non-taxane-containing regimens for advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC): A systematic review.
Authors: Behera Madhusmita , Pillai Rathi Narayana , Owonikoko Taofeek Kunle , Kim Sungjin , Chen Zhengjia , Saba Nabil F. , Belani Chandra Prakash , Khuri Fadlo Raja , Ramalingam Suresh S.
Published: March 2020

e19094

Background: In pre-clinical studies, the efficacy of anti-angiogenic agents depends on the specific chemotherapy given in combination. This appears to result from abrogation of activated circulating endothelial progenitor cells by cytotoxic agents, with the most favorable results noted with the combination of anti-angiogenic therapy with taxanes. We conducted a systematic review of published clinical trials that evaluated the efficacy of bevacizumab in combination with taxane or non-taxane containing regimens for untreated, non-squamous NSCLC patients. Methods: An extensive search of published clinical trials was conducted from electronic databases (MEDLINE, EMBASE, Cochrane) and meeting proceedings using relevant search criteria. Single arm phase II studies or randomized trials reporting the efficacy of bevacizumab combined with taxane or non-taxane regimens were selected. A systematic analysis of extracted data was performed using Comprehensive Meta Analysis (Version 2.2.048) software under the random effect model. Clinical outcome in patients treated with taxane versus non-taxane regimen was compared using point estimates for weighted values of median overall survival (OS), progression free survival (PFS), and response rate (RR). Results: Twenty-five studies reported between 2005-2013 were eligible. A total of 4,279 patients (1663 and 2616 in the taxane and non-taxane groups respectively) were included. The most common chemotherapy agents used with bevacizumab among non-taxane regimens were gemcitabine (65%), vinorelbine (12%) and pemetrexed (11%). The weighted median age of the population was 59 years (Males-60%; Adenocarcinoma-82%; ECOG performance status 0/1(%)- 39/58). The weighted median OS was 15.1 vs. 13.7 months (p= 0.07); PFS was 7.4 vs. 7.1 months (p=0.27); RR was 39.6% vs. 37.7% (p=0.29) for taxane and non-taxane groups respectively. Conclusions: The combination of bevacizumab with taxane containing regimens is associated with a trend towards improved survival, but not RR and PFS, over non-taxane regimens for first-line therapy of advanced non-squamous NSCLC.
Baseline characteristics from two ongoing phase III trials for the prevention and treatment of muscle wasting in NSCLC.
Authors: Steiner Mitchell S. , Gralla Richard J. , Prado Carla M. M. , Hancock Michael L. , Dalton James T. , Johnston Mary Ann , Crawford Jeffrey
Published: March 2020

e19100

Background: Although muscle wasting and cancer cachexia occur in > 80% of patients with advanced cancer, few well-powered scientifically-based trials have been conducted. Using enobosarm, a novel SARM, we have now enlisted 650 patients (pts) with advanced NSCLC in two phase III trials. Recent studies indicate major advantages for supportive care in NSCLC at chemotherapy initiation (Temel, NEJM 2010).This presentation examines the feasibility of pt enlistment at chemo initiation, the major characteristics of these pts and trial design for the prevention and treatment of muscle wasting. Methods: Both double-blind, placebo-controlled, international trials evaluate the effect of enobosarm in NSCLC. ˜300 pts with stage III or IV NSCLC were randomized in each trial at initiation of first-line chemo to receive additionally enobosarm or placebo for 5 months. Pts were males and postmenopausal females ≥30 years, ECOG ≤1. First line chemo: a platinum + taxane (Power 1) or platinum + non-taxane (Power 2). Co-primary endpoints at Day 84 are physical function assessed by stair climb power (SCP) and lean body mass (LBM) by DXA. Baseline characteristics are available on 634 pts (98%), as in the Table. Results: See Table. Conclusions: These results indicate that it is feasible to enlist pts receiving first-line chemo in trials designed to prevent or treat muscle wasting and cachexia; their presenting characteristics are typical for NSCLC. Median weight loss at baseline was 5% even though weight loss was not required for study inclusion. LBM and SCP were lower than typically observed in healthy individuals indicating significant functional decline before starting chemo for NSCLC. These phase III trials will determine the effect of enobosarm on preventing and treating muscle wasting in NSCLC. Clinical trial information: NCT01355484 and NCT01355497. [Table: see text]
Exploratory modeling and simulation to support development of motesanib in Asian patients with non-small cell lung cancer (NSCLC) based on MONET1 study results.
Authors: Bruno Rene , Hsu Cheng-Pang , Claret Laurent , Lu Jianfeng , Sun Yu-Nien
Published: March 2020

e19103

Background: Motesanib failed to improve overall survival (OS) in the MONET1 phase III study when combined to carboplatin/paclitaxel (CP) vs. CP in first-line NSCLC cancer patients (JCO 30:2829-2836, 2011). However, outcome of the study was favorable in a sub-population of Asian patients. We performed exploratory modeling and simulations based on the MONET1 data in order to support further development of motesanib in Asians. Methods: We developed 1) a longitudinal tumor growth inhibition model to estimate time to tumor regrowth (TTG)) using data from 934 out of 1,090 (86%) included in MONET1 and 2) a multivariate parametric model for OS including baseline prognostic factors and tumor size metrics to capture treatment effect. OS model was assessed in simulating OS distribution and hazard ratios (HR) in multiple replicates of MONET1 and comparing 95% predictive distribution (PI) with observed data. Multiple replicates of virtual phase III studies in Asian patients were simulated to assess probability of success of alternative designs. Results: Baseline tumor size (TS) and smoking history (former and current smokers vs. never smokers) were significant independent prognostic factors for OS with Asian ethnicity and log (TTG). Logarithm of OS (in days) was defined by a linear model. Parameter estimates of the OS model are given below (Table). The model successfully predicted OS distributions and HR in the full populations and in Asian patients. Simulations suggested that a 500 patient phase III study would exceed 80% power to demonstrate motesanib combination OS superiority in Asian with an expected HR of 0.74. Conclusions: A model-based estimate of TTG captured treatment effect in Asian and simulations suggested superiority of motesanib combination in these patients. The OS model could be used to simulate expected OS based on longitudinal NSCLC tumor size data with new investigational agents and support development decisions and study design. [Table: see text]
Achieving patient health outcomes via CME: A case-study in educating oncologists in the treatment of non-small cell lung cancer.
Authors: Bregartner Tom
Published: March 2020

e19104

Background: The Validation Model is an educational series built on the concept of strengthening education by incorporating the patient perspective. After conducting two iterations of the Validation Model to educate oncologists in the treatment of NSCLC, Quintiles Medical Education was able to demonstrate that CME can lead to improved patient health outcomes by changing physician behaviors in practice. Educational measurement tools, including chart audits, revealed an increase in tumor histology and EGFR mutation testing. Histologic and molecular marker testing leads to optimization of treatment based on tumor pathology and genotype, respectively, as per NCCN guidelines. Personalization of treatment according to guidelines results in improved health outcomes. Methods: The Validation Model consisted of 6 educational activities for which efficacy was measured by conducting pre- and post-tests of knowledge and clinical competence among participants. Participants were then asked to complete a follow-up survey which was designed to determine if specific practices had been implemented since participation. The self-self reported behavioral data was validated by the distribution of patient surveys, designed to measure patient satisfaction and expectation with care, and chart audits, designed to determine the actual practice habits of the participating practitioners. Results: More than 500 participants have completed all 6 of the educational activities. The activities have demonstrated improved knowledge and competence in the educational setting and changes to clinical practice and, as a result, patient health outcomes. Conclusions: CME can be used as an effective tool to improve patient health outcomes in the treatment of NSCLC.
Treatment of advanced recurrent NSCLC with daily oral vinorelbine: A phase I trial.
Authors: Tufman Amanda , Borgmeier Astrid , Guetz Sylvia , Von Pawel Joachim , Rittmeyer Achim , Huber Rudolf M.
Published: March 2020

e19108

Background: Metronomic regimens, in which small, frequent doses of chemotherapy are administered, have been suggested to lower toxicities while maintaining, or even improving, efficacy. The high frequency of administration aims to expose the tumor continuously to the drug, thereby preventing the recovery of malignant cells between cycles. Previous studies have shown that the administration of oral vinorelbine thrice weekly is feasible and well tolerated. We present a phase I dose finding study in which a regimen of daily oral vinorelbine was evaluated in pretreated patients with advanced NSCLC. Methods: Pretreated patients with advanced NSCLC were treated with vinorelbine (Navelbine oral) at fixed daily doses of 20 mg, 30 mg, 40 mg or 50 mg for 21 days of each four-week cycle. The primary end point was the identification of the maximum tolerated dose, which was reached when two out of six patients experienced dose limiting toxicity (DLT) in cycle 1 or 2. Results: 27 patients with advanced NSCLC (78% stage IV, median age 65 y) were enrolled. Most (93%) had received previous systemic therapy (mean: 2.6 lines). Daily administration of oral vinorelbine was well tolerated up to 30 mg/d without any DLT. At 40 mg one of three patients experienced DLT in cycle 1 and another patient in cycle 2. Three out of six patients had DLT at the dose level of 50 mg. Therefore, the recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2 if no DLT had occurred. Eleven patients (2 out of 7 treated with the recommended dose) experienced treatment-related toxicities of grade 3 or higher. The adverse events were primarily hematological (febrile neutropenia: 14.8%, leukopenia: 29.6%, lymphopenia: 18.5%, neutropenia: 18.5%). One patient died as a result of colitis. The frequency of non-hematological toxicities of grade 3 or higher was low with only single cases reported for nausea, fatigue, neutropenic sepsis, pneumonia, increased gamma-glutamyltransferase and anorexia. Conclusions: Daily administration of oral vinorelbine in pretreated patients is feasible and safe. An initial dose of 30mg/d is well tolerated and can be increased to 40mg/d in cycle 2. Further studies are warranted to evaluate the efficacy and safety of this novel approach. Clinical trial information: EudraCT number 2006-001573-25.
Radiotherapy for intubated patients with malignant airway obstruction: Futile, or facilitating extubation?
Authors: Louie Alexander V. , Lane Sophia , Palma David , Warner Andrew , Cao Jeffrey Quoc , Rodrigues George
Published: March 2020

e19120

Background: There is uncertainty as to the appropriate management of intubated patients with malignant airway obstruction (MAO). Radiotherapy (RT) may be delivered but requires substantial resources in this patient population. In the absence of evidence, it is unknown if radiotherapy facilitates extubation or prolongs ICU stays, resulting in a delay in the appropriate transition to end-of-life care. Methods: We performed a 10-year retrospective review of patients in the ICU treated with RT for MAO. Primary study endpoints were overall survival (OS) and extubation success (ES) defined as ≥48 hours without reintubation or death. Secondary endpoints included rates of discharge from the ICU and to home. Logistic regression and Cox regression analyses were performed to identify factors associated with ES and OS. Results: Twenty-six patients were eligible for analysis. Patients waited an average of 2.9 days (±4.5) from intubation and MV until receiving RT. Seven patients (27%) achieved ES, occurring between days 4 and 22 after RT initiation. All of these patients were discharged from the ICU, and most (n=6) were discharged home. There was a trend for a higher chance of ES in patients who received higher radiation doses (OR per 5 Gy increase: 0.63, p = 0.080). Median OS was only 0.36 months (range 0–113 months), and 6-months OS was 11%. On Cox regression analysis, increased radiation dose was predictive of improved OS (HR per 5 Gy increase: 0.74, p = 0.016). Conclusions: Although median survival is short, in a minority of intubated patients with MAO, RT is associated with ES. Survival beyond six months is uncommon, although improved OS is associated with higher delivered doses of RT.
An assessment of clinical and economic outcomes of U.S. veteran lung cancer patients.
Authors: Fritschel Elyse , Wang Li , Li Lu , Zhang J , Baser Onur
Published: March 2020

e19122

Background: More people die from lung cancer in the United States than any other cancer type, and despite improvements in survival for other cancer types, 5-year lung cancer survival has remained low (Centers for Disease Control and Prevention. Lung Cancer. Available at www.cdc.gov/cancer/lung. Accessed February 04 , 2013; Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008; 8(3): 819-31.). This study aimed to describe the outcomes of lung cancer patients in the U.S. Department of Veterans Affairs (VA) population. Methods: A retrospective study of patients diagnosed with lung cancer during the study period of October 1, 2005 to September 30, 2010 was conducted using the Veterans Health Administration datasets. Lung cancer patients were identified using International Classification of Disease 9th Revision Clinical Modification (ICD-9-CM) diagnosis code 162.xx. Descriptive statistics were calculated as means ± standard deviation (SD) and percentages. Comorbidities were measured for the 1-year baseline period before the disease identification date. Health care costs and utilization were measured for the 1-year follow-up period after the identification date. Results: In patients identified with lung cancer (n=73,150), common comorbidities included hypertension (n=21,377, 29.22%), chronic airway obstruction (n=14,305, 19.56%), abnormal findings on radiological and other lung field examination (n=12,437, 17.00%), and diabetes (n=11,569, 15.82%). Nearly half of all lung cancer patients had follow-up inpatient visits (46.47%), which translated to an average inpatient cost of $21,420 annually per patient. Nearly every patient studied had at least one follow-up outpatient visit (99.11%), and the average cost per patient totaled $12,986 annually ($12,110 for outpatient office and $411 for outpatient ER service costs). Conclusions: Inpatient and outpatient visits result in considerable health care costs for veteran lung cancer patients. Comorbid conditions are also relatively frequent in this population. Further research could elucidate economic outcomes for lung cancer patients by comorbidity severity.
Less toxic chemotherapy on the uptake of all lines of chemotherapy in advanced non-small cell lung cancer: A 10-year retrospective population-based review.
Authors: Ho Cheryl , Ramsden Katherine , Murray Nevin , Sun Sophie , Melosky Barbara L. , Laskin Janessa J.
Published: March 2020

e19131

Background: The platinum doublet is standard first-line therapy in advanced NSCLC. Over the past decade, well-tolerated second-line therapies have been approved, including erlotinib and pemetrexed. We hypothesize that the introduction of less-toxic chemotherapy has increased treatment of advanced NSCLC, resulting in improved survival. Methods: The BC Cancer Agency provides cancer care to a population of 4.5 million. A retrospective review was conducted of all referred stage IIIB/IV patients in four 1-yr time cohorts; C1 baseline (1998) and 6 months after the provincial approval of C2 docetaxel (2001), C3 erlotinib (2006) and C4 pemetrexed (2007). Results: 2,623 patients were referred and 720 had systemic therapy. Characteristics: M/F 55%/45%, median age 67 (33-101), ECOG <=1/>=2/unknown 33%/56%/11%, never/former/current/unknown smoker 9%/35%/36%/20%, squam/nonsquam/NOS 18%/41%/41%. More patients received first-line chemotherapy over time; 16%, 23%, 34%, 33% C1-4 respectively. In C1 to C4 uptake of second line (21%, 27%, 38%, 55%) and third line (10%, 10% 14%, 18%) increased. In C1 the most common first-line doublet was cis/vino (70%) and in C4, cis/gem (45%). Second-line doce was frequently used in C2 (51%) but usage decreased in C4 to 7% vs. erlo 50% and pem 26%. In the >=70 group (n=1,118), first-line usage increased from C1 9% to C4 19% and second-line in the C2 (doce) 4% to C4 (erlo+pem avail) 56%. The increased use of systemic therapy was associated with improved survival in all patients: C1 4.56 m vs C4 4.98 m (p=0.004) and treated patients; C1 9.48 m vs C4 12.07 m (p=0.014) and the >= 70 group; C1 9.7 m vs C4 12.5 m (p=0.07). Conclusions: This population-based data set represents the trend of treatments over time in a large geographical area, including community and tertiary care cancer treatment sites. The introduction of less-toxic systemic therapy for advanced NSCLC resulted in an increased proportion of patients treated with first-line chemotherapy and an even greater increase in second-/third-line treatment. This trend was particularly evident in the elderly. Associated with this was a significant improvement in overall survival for all subsets.
Phase Ib extension study of eribulin mesylate in combination with carboplatin in patients with chemotherapy-naive advanced non-small cell lung cancer (NSCLC).
Authors: Raftopoulos Harry , Aisner Joseph , Kumar Kirushna , Goel Sanjay , Dittrich Christian , Jain Minish , Gopalakrishna Prashanth , Salazar Paloma , Jones Beverley , Petrylak Daniel Peter
Published: March 2020

e19145

Background: Eribulin mesylate as monotherapy has shown antitumor activity in patients with advanced NSCLC that progressed during or after platinum-based doublet chemotherapy (Spira AI et al. Clin Lung Cancer 2012; 13:31-38.). Following evidence of additive activity with eribulin and carboplatin in lung cancer cell lines, a phase Ib, dose-escalation study determined the maximum tolerated dose and optimum administration sequence of the combination as eribulin mesylate 1.1 mg/m2 (0.97 mg/m2 eribulin as free base) followed by carboplatin AUC 6. We report results from an extension arm that investigated the efficacy and safety of this combination in chemo-naïve patients with advanced NSCLC. Methods: Chemo-naïve patients with histologically or cytologically confirmed advanced NSCLC (stage IIIB or IV) with measurable disease were enrolled. Eribulin mesylate was administered intravenously (i.v.) on days 1 and 8 every 21 days, along with carboplatin i.v. on day 1. Efficacy assessments included best overall objective response rate (ORR; RECIST), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and duration of response (DOR). Adverse events (AEs) were also recorded. Results: 12 patients were accrued (11 male, 1 female) with a median age of 66.5 (range 42-74) years. For the 11 patients evaluable for efficacy, overall ORR was 27.3% (all partial responses) and DCR was 63.6%. Median (range) OS was 12.1 (1.6-12.1) months (5 patients still alive); PFS was 4.2 (0.03+-5.8+) months (upper value censored as 1 patient still responding at final visit); and DOR was 2.9 (2.8-3.1+) months. The most common AEs ≥grade 3 were thrombocytopenia (n=6), neutropenia (n=5), febrile neutropenia (n=4), anemia (n=3), and dyspnea, hypokalemia, leukopenia, and pneumonia (n=2 each). Conclusions: The combination of eribulin and carboplatin yielded no unexpected safety findings. Given the evolving treatment practices for NSCLC, further studies involving larger numbers of patients are warranted, with consideration given to specific histologic subgroups. Clinical trial information: NCT00268905.
Clinical benefit of second EGFR-TKI retreatment on overall survival in patients with advanced non-small-cell lung cancer harboring EGFR-mutation positive after failure of the initial EGFR-TKI treatment: A retrospective analysis.
Authors: Nakashima Masanao , Hirose Takashi , Oki Yasunari , Murata Yasunori , Sugiyama Tomohide , Ishida Hiroo , Okuda Kentaro , Yamaoka Toshimitsu , Ohmori Tohru , Ohnishi Tsukasa
Published: March 2020

e19164

Background: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) bring the best result to EGFR-mutation positive non-small cell lung cancer patients, but most lead to drug resistance. These acquired resistances are associated with T790M mutation or Met amplification, HGF expression. To assess whether affects overall survival in these patients, we did a retrospective study comparing survival outcomes in 2nd EGFR-TKI treated patients with controls without 2nd EGFR-TKI screened during the same time period. Methods: We examined overall survival in thirty-two of 52 patients with advanced, EGFR-mutation-positive NSCLC who treated 1st EGFR-TKI (gefitinib) from January 2009 to December 2012. We identified 16 patients who were given 2nd EGFR-TKI (erlotinib) after failure of the initial gefitinib treatment (retreatment group) with 16 patients who were not given 2nd EGFR-TKI but given only chemotherapy (control group), 20 patients who might treat with 2nd EGFR-TKI or chemotherapy at that time were excluded in progress after failure of the initial gefitinib treatment. To assess differences in overall survival, we assessed subsets of clinically comparable 2nd EGFR-TKI retreatment group. Results: Among 16 patients who were given 2nd EGFR-TKI, retreatment group who were given one or two cytotoxic chemotherapy from 1st EGFR-TKI to 2nd EGFR-TKI, median overall survival from initiation of the diagnosis with advanced IIIB/IV stage or surgical recurrent NSCLC was 24.2 months. 16 patients of control group who were given from second to seven line cytotoxic chemotherapy, overall survival was 15.8 months (p=0.021). Retreatment group who were given 2nd EGFR-TKI was significantly longer than control group in EGFR mutation positive patients. Response rate and disease control rate with 2nd EGFR-TKI retreatment are 12.5% and 31.3%. Conclusions: In patients with advanced, EGFR mutation positive NSCLC, retreatment group who were given 2nd EGFR-TKI therapy was associated with improved survival compared with control group who were given only cytotoxic chemotherapy.
The efficacy of PEG-Asp-argase-based chemotherapy for nasal-type extranodal NK/T-cell lymphoma.
Authors: Wen Jing-Yun , Li Mai , Li Xing , Lin Qu , Dong Min , Ruan Dan-Yun , Wu Xiang-Yuan
Published: March 2020

e19504

Background: Nasal-type extranodal NK/T-cell lymphoma (ENKL) is a highly invasive disease with quite poor prognosis.Pegaspargase (PEG-Asp) displays a similar anti-cancer mechanism as that of L-asparaginase (L-ASP), but exhibits lighter antigenicity. The aim of the present research was to evaluate efficacy and safty of PEG-Asp-based regimen in ENKL. Methods: Data were collected from 23 patients with histologically confirmed ENKL who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to March 2012. Each patient received PEG-Asp 2500 IU/m2/IM on day 1 of each 21-day chemo-cycle. Among them, 8 received combination chemotherapy with CHOP regimen, 11 with EPOCH, and 4 with a CHOP-like regimen (CHOP + bleomycin). The CHOP regimen consisted of cyclophosphamide 750mg/m2, IV (day 1), pirarubicin 40mg/m2, IV (day 1), vincristine 1.4 mg/m2, IV (day 1), and prednisone 100mg, oral (days 1- 5). The EPOCH regimen consisted of etoposide 50mg/m2, epidoxorubicin 12 mg/m2 and vincristine 0.4mg/m2 dissolved in 500mL saline and administered as a continuous IV drip for 24 hours on days 1- 4. Cyclophosphamide 750mg/m2, IV (day 5) and prednisone 60mg/m2, oral (days 1-5), were also administered. In the CHOP-like regimen, bleomycin 15mg was added on days 1-3. Stage I-II patients received local radiotherapy after the chemotherapy. Results: The patients received the PEG-Asp-based chemotherapy for 2-5 cycles (median, 4 cycles). Eleven (47.8%) achieved complete response (CR), and the overall response rate (ORR) was 82.6%. The median time to progression (TTP) was 5 months (range, 2-6 months) and the median OS was 16 months (range, 5-38 months). The 1-year and 2-year survival rate were 82.6% (19/23) and 56.5% (13/23) , respectively. A minor glutamic-pyruvic transaminase (GPT) elevation was observed in 3 patients (13.0%), slight decrease of albumin in 3 (13.0%), reduced fibrinogen level in 2 (8.7%), grade I-II WBC bone marrow suppression in 8 (34.8%), and grade III-IV WBC bone marrow suppression in 3 (13.0%). No allergic incidences were witnessed. Conclusions: Our results suggested PEG-Asp-based chemotherapy presented potential effects in treating nasal-type ENKL with acceptable side effects profile.
Epidemiologic findings of non-Hodgkin lymphoma (NHL) in Puerto Rico (PR).
Authors: Ortega Jose Luis , Tirado-Gomez Maribel , Cabanillas Fernando , Rivera-Rodriguez Noridza , Torres Carlos , Ortiz Karen
Published: March 2020

e19505

Background: NHL was the 6th leading cause of cancer among USA Hispanics from 2005-2009. There is limited literature about lymphoma among Hispanics outside USA. The goal of this study is to assess the incidence, trends, survival and histological distribution in a population of Puerto Ricans and compare the results with USA. We report data on 3,184 pts diagnosed with lymphoma from the PR Cancer Center Registry during 2004-2009. Methods: Rates of sex-specific, age-adjusted incidence (AAIR) with 95% CI were estimated and standardized by age-adjustment according to the world standard population. The annual percent change (APC) using joint point regression analysis was determined. Data was compared with the SEER Cancer Statistic Review (1975-2009). Results: NHL comprises 82% of lymphomas in PR. As in USA it is the 6th most common cancer in males and the 7th in females. AAIR per 100,000 for NHL in PR was lower as compared to USA: 11.8 for males in PR vs 23.2 in USA, while for females it was 9.8 in PR vs 16.2 in USA. Despite a lower AAIR, there was an increase of 3.2% APC in NHL for PR during 2004-09. When analyzed according to gender, this rise was attributed only to females: 6.3% increase vs 0.5% in males. In contrast, in USA a decreasing trend in APC (-0.8%) was seen for females. B cell lymphomas in PR comprise 92% of NHL and 90% in USA. DLBCL represents 53% of all B cell-NHL in PR which is markedly higher than the 28% reported in USA. Follicular NHL in PR represents 22% of all NHL, in contrast to 32% in USA. There is a noticeable difference in the distribution of T cell lymphoma subtypes in PR as compared with USA, with a higher number of cases of anaplastic large cell and cutaneous T cell lymphomas and a lower frequency of angioimmunoblastic T cell lymphomas in PR. In terms of relative survival rate (RSR), our results are comparable to USA. Follicular NHL has a 5 year RSR of 74% in PR vs 75% in USA and DLBCL has a 5 year RSR of 47% in PR, vs 50% RSR in USA. Conclusions: Despite a lower AAIR, a significant increasing trend of NHL was observed in PR and we determined this to be exclusively observed among females. We also identified marked differences between the distribution of histologic subtypes of NHL in PR and USA. We plan to assess which histologic subtypes are increasing and in which regions of the island.
MicroRNA profiles (including 370 miRNAs) in lymphomas.
Authors: Paydas Semra , Acikalin Arbil , Ergin Melek , Celik Hikmet , Yavuz Basak , Tanriverdi Kahraman
Published: March 2020

e19512

Background: MicroRNAs (miRNAs) are small noncoding RNAs and they control the expression of protein-coding genes. Deregulation of miRNAs has been found to be associated with the pathogenesis and prognosis of various diseases including malignant tumors. In this study cancer related 370 miRNAs, which are most commonly related with cancer, have been explored in 88 cases with diffuse large B cell lymphoma (DLBCL) and 32 cases with Hodgkin’s lymphoma (HL). Sixty samples taken from cases with reactive lymphadenopathy have been used as control. Quantitative miRNA results were compared with lymphoma entities and also with controls. Methods: Samples taken from 88 cases with DLBCL and 32 cases with HL were used as study material. QPCR method was used to profile 370 miRNAs. Biogazelle qbasePLUS 2.0 software was used for analysis of the results. Global mean normalization method used for normalization of the individual miRNA expression levels. Mann-Whitney U test was used and p>0.05 was evaluated as statistically important. Results: miR -41-5p, miR-494, miR-10a-5p, 340-5p, miR-155-5p, miR-500a-5p, miR-148b-3p, miR-330-3p, miR-191-5p, miR-193b-3p, miR-92a-3p, miR-34a-5p, miR-99b-5p, miR-671-3p were found to be increased in cases with DLBCL as compared with controls. miR-370, miR-155-5p, miR-372, miR-93-5p, miR-324-3p, miR-34a-5p were found to be increased in cases with HL as compared with controls. miR-320a, miR-889, miR-126-3p, miR-370, miR-138-5p, miR-29a-3p, miR-339-3p, miR-93-5p, miR-324-3p, miR-345-5p were found to be increased in cases with DLBCL as compared with HL. Conclusion: miRNA profile of DLBCL has been previously studied. However there is limited information about miRNA profile of HL. Our method for miRNA profiling is qPCR and it is the gold standard for miRNA profiling currently. Studies which has comprehensive numbers of miRNAs are mostly microarray based studies. Becuase of short sequence of miRNAs, microarray method doesn’t perform as good as in gene expression studies especially in low expressed miRNAs. In our best knowledge our study is the most comprehensive qPCR miRNA profiling study in HL and NHL. In further step we would like to compare miRNA profile and clinic-prognostic parameters.
Prevalence of autoimmune conditions in patients with Waldenstrom macroglobulinemia: Exploratory analysis of a series of consecutive patients.
Authors: Atienza Jonessa , Codreanu Ion , Varilla Vincent , Reale Michael A. , Silver Joel , Pazooki Mohammad , Dasanu Constantin
Published: March 2020

e19514

Background: Literature suggests association between Waldenström macroglobulinemia (WM) and autoimmune conditions which may share the same pathogenesis. We identified the prevalence of autoimmune phenomena in WM patients and compared it with the general population. Methods: We conducted retrospective and prospective analyses in a series of patients (n=12) with WM followed in outpatient setting. The median age was 74 years. The charts were reviewed for autoimmune abnormalities; length of prospective analysis segment was circa 24 months. The prevalence of autoimmune disorders was compared with the general population. Statistical analysis: Findings were tested for statistical significance using Fisher’s exact test for small number of observations (95% confidence); p value < 0.05 considered significant. Results: Circa 58.3% patients had autoimmune disorders (Table). These include Hashimoto thyroiditis, pernicious anemia, immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), chronic inflammatory demyelinating polyneuropathy (CIDP), pure red cell aplasia (PRCA), polymyalgia rheumatica (PMR), temporal arteritis, and ANA positivity. The Table summarizes the statistical analysis of each autoimmune condition with their respective p values. Conclusions: More than 50% of patients had autoimmune conditions, significantly exceeding overall prevalence in general population. Statistically significant differences noted for pernicious anemia, Hashimoto thyroiditis, ITP, AIHA, CIDP, PRCA, and temporal arteritis. The difference was not significant for PMR and ANA positivity. However, analysis of larger cohorts is needed to confirm our observations. [Table: see text]
Feasibility of highly intensive chemotherapy for AIDS-related Burkitt lymphoma.
Authors: Kojima Yuki , Moritani Suzuko , Nakamura Hiroyuki , Yamamoto Hideyuki , Miyata Yasuhiko , Iida Hiroatsu , Ohashi Haruhiko , Nagai Hirokazu
Published: March 2020

e19521

Background: Burkitt lymphoma (BL) progresses very rapidly, but highly intensive chemotherapy (e.g. CODOX-M/IVAC, hyper-CVAD/MA) has been shown to be a promising strategy. In this time, AIDS-related lymphoma is treated with similarly to non-AIDS lymphoma, nevertheless it is not clear whether the highly intensive regimens are feasible and beneficial for AIDS-related Burkitt (AIDS-BL) or not. The purpose of the current study is to compare the toxicity of AIDS-BL to non-AIDS-BL retrospectively. Methods: We collected the data of all patients (pts) with BL between 2004 and 2011 at our institution. Chart review was performed for all identified pts. The effects of treatment and the clinical variables on overall survival (OS) were assessed. Results: We identified 25 Burkitt lymphomas, and a total of 108 cycles of highly intensive chemotherapy were administered. Nine of these 25 were AIDS-BL (median age, 51; range, 36 to 68) and 16 were non-AIDS-BL (median age, 60; range, 27 to 75). As chemotherapeutic regimens, 15 (60%) were treated with CODOX-M/IVAC, 8 (32%) with hyper-CVAD/MA, and 2 (8%) with EPOCH. Of 12 pts (48%) treated with rituximab-contain regimens. Completion rate of planned chemotherapy was 64%. The median follow-up was 34.3 months. Three-year OS was 73.6%. There were no significant differences in OS between chemotherapeutic regimens (p=0.94) and between AIDS-BL and non-AIDS-BL (p=0.39). The overall incidence of grade 3/4 febrile neutropenia was 64.8% (70 of 108 cycles), 60.5% for HIV-infected and 67.7% for HIV-negative case, respectively. Grade 4 thrombocytopenia was frequently observed in AIDS-BL (72.1% vs. 40.0%), and incidence of grade 3/4 anemia was not different (79.1% vs. 70.8%). Conclusions: This study showed that clinical outcomes, including toxicities, of AIDS-BL were similar to non-AIDS-BL when BL treated with highly intensive chemotherapy.
Lenalidomide and dexamethasone in overtreated multiple myeloma patients: A single center update.
Authors: Moscetti Alessandro , De Benedittis Daniela , Resci Federica , Antolino Giusy , Bianchi Maria Paola , Naso Virginia , La Verde Giacinto
Published: March 2020

e19527

Background: Lenalidomide (Len - Revlimid) is a therapeutic option for relapsed and refractory multiple myeloma, especially in association with steroids. Methods: Oraldaily lenalidomide (10-25 mg) for 21 days every month (median courses 9.7) and weekly dexamethasone (Dex) were administered until progression in 41 pretreated patients (median age 66.2 yrs) observed between June 2008 and January 2013 at Hematology Department of Sant’Andrea Hospital in Rome. Past treatment included alkylants, anthracyclines, IFN-α, thalidomide, bortezomib and single or double autograft. Twenty five patients were evaluated after 6 courses of therapy, administered as second to fifth line, and prospectively followed-up; two patients weren’t considered because of early death. Treatment response was assessed according to IMWG uniform response criteria. Results: The overall response rate was 56% (14/25 pts) with a median duration of response of 13 months: 1 patient reached CR, 1 VGPR, 12 patients reached a partial response (PR), 10 showed a stable disease (SD) and 1 progressive disease (PD). The median progression free survival was 14.8 months. Among responder patients, 4 died due to progression disease after a median of 16.5 courses, while 9 are in continuous treatment (3 with over 33 courses each) and 1 in salvage therapy; among non responder ones, 7 died for PD, while 3 are in continuous treatment and 1 in salvage therapy. The reported side effects included pneumonia, neutropenia, diarrhea, peripheral sensitive polyneuropathy, transient liver failure, lower urinary tract infection, skin rash, transient aphasia, conjunctival hemorrhage and deep vein thrombosis, all resolved with brief discontinuance and specific support therapy without hospitalization. Conclusions: This study shows that Len-Dex combination is an effective oral salvage therapy with good response rate and manageable side effects for relapsed and refractory multiple myeloma patients.
Morphologic pattern of CD30 distribution within neoplastic cells in Hodgkin lymphoma.
Authors: Paszkiewicz-Kozik Ewa , Rymkiewicz Grzegorz , Osowiecki Michal , Romejko-Jarosinska Joanna , Walewski Jan Andrzej
Published: March 2020

e19535

Background: CD30 protein is expressed on Hodgkin and Reed-Sternberg (HRS) cells in nearly all cases of classical Hodgkin lymphoma (HL). CD30 is present on a cell membrane and on the Golgi complex of the endomembrane cell system. Given the growing clinical application of CD30 targeting we were interested to see if there is variability in distribution of CD30 protein between the cell surface and the cytoplasm. External exposure of CD30 is most likely a critical condition of successful interaction with the ligand and possibly, a predictive factor for response to CD30 antibody. To our knowledge, clinical data on CD30 expression have not yet been published in the context of cell topography. Methods: The CD30 protein was evaluated in formalin-fixed paraffin-embedded (FFPE) tissue sections by immunohistochemistry (IHC) with monoclonal mouse anti-human antibody CD30 (clone Ber-H2) (Dako). IHC was performed using the EnVision Plus Detection Systems LSAB kit (Dako Corp., Carpinteria, CA), and an antigen-retrieval technique was applied. Morphological pattern (localization of CD30) of CD30 expression was evaluated in each case under a microscope examination. Results: FFPE tissue specimens from 83 newly diagnosed and relapsed (n=78 and n=5, respectively) HL patients were examined. The average (range) of patient age was 39 (18-89), male/female ratio was 1/0.88. Histological subtypes of HL were nodular sclerosis in 87%, mixed cellularity in 8%, lymphocyte rich in 3% of cases, and 1 case of lymphocyte-depleted classical HL. Immunophenotype was typical of classical HL, and HRS cells were positive for CD30 in all cases. Immunostaining for CD30 was present on the Golgi body in 98% of cases, and it was demonstrated on the cell membrane in 27% of cases. Conclusions: In our series of 83 patients with classical HL, predominant pattern of CD30 expression was cytoplasmic (Golgi body), and only 27% of cases demonstrated cell surface expression. We hypothesize that cell surface expression of CD30 protein might predict a response to anti-CD30 antibody that is in the order of magnitude of 30% complete remissions in recurrent HL.
Early lymphocyte recovery (ELR) impact on disease outcome following autologous hematopoietic stem cell transplantation (HDT/ASCT) for multiple myeloma (MM) in the era of novel agents.
Authors: McDuffie Jeremy Scott , Savani Bipin N. , Chinratanalab Wichai , Goodman Stacey , Greer John P. , Oluwole Olalekan O. , Engelhardt Brian G. , Jagasia Madan H. , Kassim Adetola
Published: March 2020

e19539

Background: Absolute lymphocyte count (ALC) > 500 cells/ µL on day 15 (ELR+) after HDT/ASCT, has been reported to be an independent prognostic indicator, for improved OS and PFS in patients with MM. Novel agents (immunomodulatory drugs (IMiDs) and proteasome inhibitors), mediate there effect through T-cell stimulation, NK cell activation, anti-proliferation, and are now main stay of therapy for MM. We sought to determine their effects on ELR, and correlated to disease outcome. Methods: A retrospective review of all MM patients seen at our institution undergoing HDT/ASCT from January 2008 to December 2012 was performed. Patients were identified from our CIBMTR database. ALC was determined pre-HDT/ASCT (T1), on day15 (T2) and d30 (T3) post-HDC/ASCT. No restrictions on inclusion were made based upon the International Myeloma Working Group response criteria. All had novel agents as part of their initial induction regimen. Disease response was determined by standard clinical and laboratory CIBMTR response criteria, and minimal residual disease status (MRD) by multiparameter flow cytometry. Results: In our study (n= 184), 52/184 patients had ELR+ while 132/184 had ALC < 500 cells/mL (ELR-) at T2. 21% received IMiDs, 33% proteasome inhibitor and 46% combination therapies. 52% of the ELR+ patients were MRD negative (-) at T1, and improved to 74% and 89% at D100, and 1 year post-HDC/ASCT respectively. Similarly 63%, 70%, and 80% of the ELR- patients, were MRD (-) at similar time-points. Chi squared analysis showed no significant difference in rates of MRD (-) based on ELR. ELR also had no impact on disease status as determined by CIBMTR response criteria, or 1 year PFS and OS (p = 0.383), (p = 0.577) respectively. Multivariate analyses, using cox-regression showed no impact of ALC at T1, T2, T3, age, sex, race, cytogenetic risk, or disease stage on disease outcome. Conclusions: Novel agents improve disease control independent of ELR following HDC/ASCT. Understanding their biologic effect on immune-reconstitution will provide a platform for adoptive immunotherapy to better target minimal residual disease.
Assessment of viable cells as a predictor of response in soft tissue sarcomas treated with neoadjuvant therapy.
Authors: Batista Ranyell Spencer Sobreira , Aguiar Samuel , Cunha Isabela Werneck , Lopes Ademar , Soares Fernando A. , Stevanato Paulo Roberto , Mello Celso Lopes
Published: March 2020

e21507

Background: Soft Tissue Sarcomas (STS) are an uncommon neoplasm with many histological subtypes with different behaviors, response to treatments and developments. The treatment of these tumors is using surgery, radiotherapy or chemotherapy. The pathological response using degree of tumor necrosis has been implicated in survival rates. However comes to assessing the degree of tumor necrosis in the surgical specimens as response parameter could be confuse because the high-grade sarcomas exhibit a high rate of necrosis even without any treatment. Methods: 31 patients with STS of high grade located in extremities treated with neoadjuvant doxorubicin and ifosfamide were observed prospectively since January 2005 to June 2011. For evaluation of surgical specimens post neoadjuvant chemotherapy, a slice of the specimen in with lower gross of necrosis was represented and after mapped evaluating grade of necrosis, fibrosis and percentage of viable cells. Results: Six patients had ≤5% of viable cells, eight had ≤10% and 12 with 30% or less in the sample. Overall survival (OS) was 100%, 100% and 91% with Disease free survival (DFS) were 100%, 85.7% and 82.5%, respectively. No patient had ≥95% necrosis in the surgical specimens considering that a large part of the tissue had fibrosis in patients with few viable cells, which do not correlate with survival. Conclusions: The viable cell count in the sample is feasible, and relates well with survival. We consider this the ideal method for response evaluation in SPM instead of counting necrosis. In combination with the literature data we suggest cutoff points of 5%, 10% and 30%.
Temozolomide metronomic schedule with weekly of cisplatin in metastaticsoft tissue sarcoma.
Authors: Shahid Tanweer , Agarwal Vikash , Basu Saumen , Bhattacharyya Gouri Shankar
Published: March 2020

e21519

Background: Dacarbazine (DTIC) is the standard treatment for metastatic soft tissue sarcoma. Temozolomide (TMZ) is a potentially attractive chemotherapeutic agent for this disease because of the oral route of administration and efficacy similar to that of dacarbazine but potential for resistance exist. Metronomic administration of TMZ might be a way to overcome resistance. Cisplatin is active against melanoma and might counteract mechanisms of resistance to TMZ. Methods: We reviewed data of metastatic soft tissue sarcoma patients treated at our Institutions with cisplatin (25 mg/m2 every 7 days for 3 out of 4 weeks) plus TMZ (50 mg/m2/day from day 2 for 27days). Our practice included such scheme for patients younger than 75 years, with a performance status not worse than 2, and adequate bone marrow, liver and renal function. Assessment of response was done every 3 cycles. Toxicity was graded according to NCI-CTC. Results: From August 2007 to September 2008, 33 patients were treated with a median age of 44 years (18–74); most frequent sites of metastases were lung (18 cases), brain and lymph nodes (11 cases each); 29 patients were treated as first-line and 4 as second-line. The median number of delivered cycles was 4 (range 2- 8). Toxicity was mild, with no grade 4 event reported. Nausea and vomiting were the most frequent and severe toxic effects: grade 3 in 2 cases and grade 2 in 10 cases, respectively. Other toxicities included thrombocytopenia (1 case grade 3 and 2 cases grade 2), anemia (1 grade 3 and 2 grade 2), neutropenia, and fatigue (1 grade 3 each). Overall, 9 patients had a partial response (27.3%; 95% exact CI: 7.0–35.5) and 8 (24%) had a disease stabilization. With a median follow-up of 20 weeks (95% CI: 19–57), there were 19 progressions and a median progression-free survival of 24 weeks (95% CI: 16-nr); 9 patients died with a median survival of 50 weeks (95% CI 43-nr). Conclusions: Results obtained in clinical practice with metronomic temozolomide plus cisplatin in the treatment of patients with metastatic soft tissue sarcoma are encouraging, in light of the negative prognostic features of treated patients.
Outcome and prognostic factors in metastatic primitive neuroectodermal tumors with uniform chemotherapy protocol: A single center experience of 150 patients.
Authors: Bakhshi Sameer , Biswas Bivas , Mohanti B. K. , Shukla N. K. , Rastogi Shishir , Agarwala Sandeep , Deo S. V. S. , Sharma Dayanand , Khan Shah Alam , Thulkar Sanjay , Vishnubhatla Sreenivas
Published: March 2020

e21522

Background: Data on metastatic primitive neuroectodermal tumor (PNET) with uniform protocol is minimal. Methods: This is single institutional patient review treated between June 2003-Nov 2011, and evaluated on intent-to-treat analysis. All patients received uniform chemotherapy (VAC/IE) as follows: neoadjuvant chemotherapy (NACT), surgery and/or radiotherapy as local treatment followed by ACT. Local treatment was offered if patient achieved CR and/or PR at both primary and metastatic site. Results: 150/374 (40%) PNET patients were metastatic with median age 15 years (range: 2–50); tumor diameter 10 cm (range: 1.8-26) and symptom duration 4 months (range: 0.1-30). Most common tumor region was pelvis 34 (23%), thorax 26 (17%) and femur in 26 (17%). Most common metastatic sites were lung only 53 (35%), bone only 35 (23%), combined bone/lung 25(17%), and bone marrow 37 (25%). Post-NACT, 9 (6%) achieved CR and 79 (53%) PR (53%) with ORR 59%. Twenty patients underwent surgery; 55 patients received radical radiotherapy following NACT. At median follow-up of 20.8 months (range: 1.6–95), 5-year EFS, OS and local control rate (LCR) were 7.6%, 15% and 37.6%, respectively. Multivariate analysis of prognostic factors in entire group and lung only metastases group is shown in the Table. Conclusions: This is the largest study of metastatic PNET from Asia and has identified unique prognostic factors. Hypoalbuminemia had inferior EFS; radical radiotherapy had inferior LCR. In group with only lung metastases, age ≤15 years and number of metastases >3 had lower EFS. In view of dismal prognosis with conventional chemotherapy in metastatic PNET, metronomic therapy may be a potential therapeutic alternative for subgroup of metastatic patients with hypoalbuminemia. [Table: see text]