bluuebunny/crossref_metadata_2025_split huggingface dataset:
NHL and rituximab biosimilar: How have prescribing behaviours changed in EU5 in 15 months?
Authors: Franceschetti Alessandra 
Published: March 2020

e19054 Background: 15 months after EMA approval of the first rituximab biosimilar to treat NHL – and 12 months on from our presentation on its initial impact at the Biosimilars Special Clinical Symposium of ASCO 2018 – this study tracks the real world impact of official endorsement on prescribing behaviour and biosimilar adoption for NHL. Methods: The Ipsos Global Oncology Monitor – an online multi-country, multi-centre medical chart review of NHL patients, where 138 geographically representative physicians provided de-identified data on 3,239 patients treated with anti-cancer drugs in France (565), Germany (379), Italy (622), Spain (684) and UK (989) from July 2017 to Sept 2018. Physicians provided diagnosis date, current and historic treatment and reasons for prescribing treatment. Data on patients treated with and without a rituximab biosimilar were compared using descriptive statistics. Results: While prescribing of the rituximab molecule was stable over the study period, prescribing of rituximab biosimilars significantly increased – from 7% to 35% (p < 0.01), most notably in Germany and UK. By Q3 2018, for those patients treated with a rituximab-including regimen (N = 483), prescribing of any EMA-approved rituximab biosimilar was 72% in Germany and 63% in UK; France, Italy and Spain reported 47%, 32% and 30%, respectively. Physicians were significantly more likely to state “Well tolerated” and “Proven efficacy” as reasons for prescribing rituximab biosimilars in Q3 2018 vs Q3 2017 (p < 0.01). Prescribing of branded rituximab in the SC formulation significantly increased, from 21% to 33% (p < 0.01). Rituxan prescribing may be partially driven by availability of the SC mode of administration (MoA) not available for biosimilars. Conclusions: Over time, prescribing of rituximab biosimilars has significantly increased in the EU5, mainly in Germany and UK. Growth is less evident in Italy and Spain, perhaps as Southern physicians are historically more averse to ‘generic’ versions. Physicians’ ongoing experience of mAb biosimilars has resulted in higher associations with “Well tolerated” and “Proven efficacy”. The rise in prescribing Rituxan with the SC MoA has likely contained an even higher prescribing of rituximab biosimilars.
Cause-specific mortality in survivors of lymphoplasmacytic lymphoma (LPL) and waldenstrom macroglobulinemia (WM).
Authors: Dalal Nicole H. , Dores Graca , Curtis Rochelle E. , Linet Martha S. , Morton Lindsay M. 
Published: March 2020

e19056 Background: LPL and WM are rare, indolent mature B-cell lymphomas. While recent studies reveal improving survival after LPL/WM, cause-specific mortality has not been comprehensively studied. Methods: We identified 6659 adults with first primary LPL (n = 2866) or WM (n = 3793) within 17 US population-based cancer registries from 2000 to 2015. Patients were followed for vital status (mean follow-up = 5.07 years), and causes of death were determined from death certificates. Standardized mortality ratios (SMRs) estimated relative risk of death compared to the general population. We estimated cumulative mortality and absolute excess risk (AER) per 10,000 person-years. Results: We observed 2826 deaths overall, of which 43%, 13%, and 42% were due to lymphoma, cancers excluding lymphoma, and non-malignant causes, respectively. There was a 20% higher risk of death due to non-malignant causes compared to the general population (n = 1194, SMR = 1.2, 95% confidence interval [CI] = 1.1 to 1.2). The most common non-malignant causes included infectious (n = 162, SMR = 1.8, 95% CI = 1.5 to 2.1, AER = 21.0), respiratory (n = 131, SMR = 1.2, 95% CI = 1.0 to 1.5, AER = 7.4), and digestive (n = 76, SMR = 1.9, 95% CI = 1.5 to 2.4, AER = 10.7) diseases. Cause-specific mortality varied by time since and age at LPL/WM diagnosis. Risks were highest in the first year after LPL/WM for non-malignant causes (SMR = 1.4, AER = 34.3), particularly infections (SMR = 2.4, AER = 34.4) and non-neoplastic hematologic diseases (SMR = 17.3, AER = 20.7). In contrast, risk of death due to cancers excluding lymphoma increased with time since diagnosis (SMR< 1y = 1.2, SMR≥5y = 1.7; AER< 1y = 15.1, AER≥5y = 60.0). Analyses by age, focused on AERs, showed generally similar risks across age groups (cancers excluding lymphoma: AER< 65= 26, AER65-75= 28, AER≥75= 31; non-malignant causes: AER< 65= 52, AER65-75= 66, AER≥75= 23). Cumulative mortality from non-malignant causes (23.7%) exceeded that from lymphoma (22.9%) beginning 9 years after LPL/WM diagnosis. Conclusions: Using population data, we identified areas to improve survivorship care of LPL/WM patients, particularly for non-malignant causes of death.
The presence of bone marrow fibrosis is associated with poorer prognosis in newly diagnosed multiple myeloma treated with immunomodulatory agents and/or proteasome inhibitors.
Authors: Paul Barry , Loitsch Gavin , Feinberg Daniel , Barak Ian , Li Zhiguo , Wang Endi , Zhao Yue , Dupuis Megan , Kang Yubin 
Published: March 2020

e19514 Background: The treatment of newly diagnosed multiple myeloma (NDMM) has evolved significantly with the advent of the immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs). While the presence of bone marrow fibrosis (BMF) has previously been associated with poor prognosis in multiple myeloma (MM), these studies were small and conducted prior to the widespread use of IMiDs and PIs. Here, we determined the incidence of BMF in NDMM patients and correlated the degree of BMF with prognosis in a population enriched for IMiD and/or PI exposure. Methods: Bone marrow biopsies from 306 MM patients seen at Duke between 2003 and 2013 were screened for BMF using a reticulin stain. Samples were scored as absent, mild, moderate, or severe fibrosis based on the degree and intensity of staining. The association between presence and degree of BMF to progression free survival (PFS) and overall survival (OS) was calculated using Kaplan-Meier analysis. Results: Of the 306 patients evaluated, 248 (81.0%) were treated with an IMiD, 241 (78.8%) were treated with a PI, and 217 (70.9%) received both. Additionally, 160 (52.3%) patients went on to receive an autologous stem cell transplant (HSCT). A total of 193 patients (63.1%) were evaluable for BMF. Of these, 96 (49.7%) had detectable BMF, while 97 (50.3%) had no BMF. The degree of BMF was mild in 60 patients (62.5%), and moderate or severe in 34 patients (35.4%). Median PFS in patients without BMF was 30.4 months, and 21.8 months in patients with BMF present (log-rank p = 0.02). Median OS was 61.1 months in patients without BMF, and 46.3 months in patients with BMF (log-rank p = 0.048). Patients with moderate or severe BMF had a particularly poor prognosis with a PFS of only 18.8 months and an OS of 32.7 months. Conclusions: Our study represents the largest dataset to date examining the incidence of BMF in MM patients, and is the only one to examine the association of BMF with prognosis in the era of novel therapies and widespread use of HSCT. Our data suggests that BMF is common in NDMM, and MM patients with BMF (particularly those with more extensive BMF) have a poorer prognosis even when treated with IMiDs and PIs. These data emphasize the importance of determining the presence and degree of BMF at time of MM diagnosis, and suggest a role for adjunctive therapies that target BMF in MM patients with co-existing BMF.
Carfilzomib-lenalidomide-dexamethasone in the management of lenalidomide-refractory multiple myeloma.
Authors: Cerchione Claudio , Martinelli Giovanni , Nappi Davide , Pareto Anna Emanuele , Di Perna Maria , Ferrara Katia , Pane Fabrizio , Catalano Lucio ,   Myeloma Cerchione Team
Published: March 2020

e19522 Background: Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, whose prognosis is particularly severe. Methods: 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43-82), median age at start of treatment 67 years (r. 48-84) previously treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2-18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. Results: According to IMWG criteria, after a median follow-up of 9 months (r. 2-18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1-4), median OS from diagnosis was 62 months (r. 9-170), median OS from start of Carfilzomib was 11 months (r. 2-18). Carfilzomib was well tolerated, with grade 2 anemia in 39% (16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion-dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2-3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Conclusions: Carfilzomib-Lenalidomide-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT.
Postoperative radiotherapy for stage II or III non–small cell lung from 1988 to 2014.
Authors: Chen Dawei , Li Yintao , Jing Wang , Yu Jinming , Xing Ligang 
Published: March 2020

e20013 Background: In 2006 ASCO, Brian E. Lally et al. reported the association between survival and postoperative radiotherapy (PORT) in patients with resected non–small-cell lung cancer (NSCLC). We now undertook a update analysis using the latest data. Methods: Updated data were obtained by the Surveillance, Epidemiology and End Results database. We analyzed stage II or III NSCLC patients diagnosed between 1988 and 2014. Results: A total of 20645 patients were selected, with a median follow-up time of 3.3 years. Predictors for the use of PORT included age less than 50 years, higher AJCC stage, T3-4 tumor stage, larger tumor size, advanced node stage, greater number of lymph nodes involved, and a higher ratio of lymph nodes involved to lymph nodes sampled. On multivariate analysis, male sex, older age, T3-4 tumor stage, N2 node stage, fewer sampled lymph nodes, higher positive lymph nodes and higher ratio of lymph nodes involved to lymph nodes sampled had a negative impact on survival. PORT had a significant adverse effect on survival, regardless of all patients (P < 0.001), or N0 subgroup ( P< 0.001) or N1 subgroup (P< 0.001). For N2 subgroup, PORT did not have a significant effect of on survival (P < 0.117). This is different from the result Brian E. Lally et al. reported in ASCO 2006. Conclusions: Postoperative radiotherapy is detrimental to resected N0 or N1 NSCLC patients and should not be used routinely for such patients. The role of postoperative radiotherapy in the treatment of N2 tumours is not clear and may warrant further research.
Umbrella study of anticancer agents in Chinese patients with NSCLC.
Authors: Zhao Xin , Xiao Liyun , Yang Yunpeng , Xie Guoyun , Fang Wenfeng , Ma Yuxiang , Zhao Hongyun , Wu Kui , Zhang Li 
Published: March 2020

e20044 Background: As the rapidly increasing of potential anti-cancer agents, it has significantly improved clinical outcomes of non-small cell lung cancer (NSCLC). However, it has been challenged by the accurately characterize the genome changes which link to the response to specific targeted therapeutics. This umbrella study aimed to provide real-world data on the efficacy of targeted therapies by multiple gene sequencing in NSCLC of Chinese population and explore for the implementation of personalized lung cancer therapy in clinical practice. Methods: This study consists of five biomarker matched arms and one non-biomarker matched arm. Within biomarker matched arms, the different cohorts will test, 1) EGFR mutation for response to gefitinib, apatinib or osimertinib; 2) ALK fusion for response to crizotinib; 3) BRAF V600E mutation for response to trametinib; 4) MET amplification for response to CT053PTSA; 5) VEGFR mutation for response to apatinib or famitinib. Within the non-biomarker matched arm, cohort will test docetaxel or carboplatin. We will perform multiple gene testing on tumor tissue, pleural fluid, plasma and peripheral blood leucocyte of all patients. Results: A total of 336 patients were enrolled in this study, including 307 lung adenocarcinomas, 27 squamous cell carcinomas, and two adenosquamous carcinomas. Approximately 40% of patients carried at least one actionable mutation. The most frequently mutated genes were TP53 and EGFR, and the percentage of EGFR mutation subtypes 19Del, L858R and T790M were 25%, 19% and 16% respectively. In addition, the mutually exclusive mutations were significantly observed between EGFR and STK11 in TP53-mut patients. All patients will be allocated a corresponding arm according to their mutated genome profile and the clinical follow-up was still in progress. Conclusions: Multiple gene sequencing could be a useful selector for personalized lung cancer targeted therapy. Furthermore, mutation coexistence and mutual exclusion might be further predictors for the risk of drug resistant, recurrence at multivariate analyzes.
The impact of heart radiation dose in lung SABR.
Authors: Gan Hao Wen, Gerald , Stobo Jon , Mohammed Nazia 
Published: March 2020

e20054 Background: Lung cancer has poor outcomes, but those patients diagnosed with stage 1 NSCLC have 5-year survival of 60-70%. Stereotactic ablative body radiotherapy (SABR) is routinely considered for patients unfit for surgery. SABR is very well tolerated hence a treatment option for patients unfit for surgery, with > G2 lung toxicity of 1.8-9.1%, but propensity-matched analyses of stage 1 NSCLC treated with surgery or SABR have shown superiority of surgery in terms of overall survival, but not lung cancer-specific survival. Excess risk of CVD is a complication of breast cancer RT, but there is limited evidence in lung cancer. The aims of this study is to investigate the impact of radiation dose to the heart in lung SABR. Methods: In a single centre from November 2011-2012, patients who treated with lung SABR outwith the “no fly zone”, using ROSEL guidelines for OARS and with the lowest or highest heart maximum point dose were selected. 9 patients in each group were analysed for dose and clinical factors retrospectively from electronic patient notes. Results: The median (range) heart dose of the high dose (HD) group was 25.3Gy (17.6–34.1) and that of the low dose (LD) group was 0.88Gy (0.18–4.8). At the end of a median follow-up of 6.7 years, OS was poorer in the HD group at 11% than the LD group at 56% (p = 0.127). While 5-year cancer-specific mortality was similar in both groups at 22%, non-cancer-associated mortality was higher in HD (44% vs 11%, p = 0.127). In addition, HD were associated with a greater risk of CV hospital admission (56% vs 11%, p = 0.131) and new cardiac abnormalities (56% vs 0%, p = 0.029). Conclusions: In this group of medically unfit NSCLC patients treated with lung SABR, there were differences in outcome possibly associated with heart dose. The HD group showed higher mortality, specifically non-cancer-related mortality and cardiac events. Investigation of a larger cohort is warranted. [Table: see text]
Potential interaction of radiation therapy, antibiotic, and steroid use in non-small cell lung cancer patients treated with checkpoint inhibitors: A retrospective analysis.
Authors: Wang Fen , D'Rummo Kevin , Al-Jumayli Mohammed , Pei Lei , Huang Chao Hui 
Published: March 2020

e20724 Background: The activity of Checkpoint inhibitors (CPI) can be predicted by PD-L1 expression. Recent studies showed that other factors can also have an impact including radiation which is beneficial but the use of antibiotics and steroids can have a deleterious effect. We performed a retrospective analysis of stage IV lung cancer patients treated with CPI at our institution and the impact of radiation treatment as well as the use of antibiotics or steroids in their outcome. Methods: We reviewed the data of 121 patients with stage IV non-small cell lung that were treated with CPI from 2015 to 2017 and analyzed the impact of PD-L1 expression, radiation treatment, steroid and antibiotic use on their progression-free survival (PFS) and overall survival (OS). We determined the use of antibiotics and steroids during any time within 30 days of initiation of treatment with CPI. Results: The median age was 66; there were 57 females and 64 males;23 current smokers, 11 non-smokers and 87 previous smokers; 87 adenocarcinomas, 24 squamous cell histology, and 10 others; 38 patients had low PD-L1 ( < 50%), 46 had high PD-L1 (≥50%) and 37 was unknown. The PFS and OS of patients treated with CPI who had radiation (RT) were not different from patients that did not have RT by Gehan-Breslow Wilcoxon test nor there was a difference based on the PD-L1 expression. The use of steroids (S) had a beneficial impact on PFS but it was numerically better but not significant on OS. Antibiotic (AB) use also had a beneficial impact on PFS and OS. Patients that had CPI as first-line therapy had shorter PFS than patients that had CPI as second-line therapy. There was no difference whether RT was used or not in patients that had antibiotics or steroids. Conclusions: Our analysis showed that several factors can potentially impact the PFS and OS of patients treated with CPI. Contrary to the previous report, the use of Ab or S did not affect adversely the PFS and OS. We did not observe a beneficial effect of RT. The sequence of use of CPI could potentially affect the PFS. This data should be taken with caution as it is a retrospective analysis with a small sample number but it reflects the real-life practice of patients treated outside of a clinical trial setting. [Table: see text]
Characteristics of T-cell receptor repertoire between lung cancer patients and healthy people.
Authors: Liang Naixin , Chen Si , Yi Yuting , Guan Yan-Fang , Xia Xuefeng , Yi Xin 
Published: March 2020

e20728 Background: Deep sequencing studies on T cell receptor (TCR) repertoire have provided a wealth of information, such as immune status, virus infection history and so on. As we all known, the thymus begins to involute at the time of birth, so does the immune system. We can use TCR sequence to describe changes in human’s immune system with age, the difference between males and females and immune stat of cancers. Methods: We analyzed TCRβrepertoire in 334 healthy individuals without cancer, aged 2–83 years, and 207 lung cancers. In detail, genomic DNA was extracted from peripheral blood and used to amplified and sequenced the CDR3 region of rearranged TCRβ genes. Finally, we got the relative frequencies of individual T cell clones. Shannon’s entropy was calculated on the clonal abundance of all productive TCR sequences. The normalized Shannon’s entropy (Shannon index) was determined by dividing Shannon’s entropy by the natural logarithm of the number of unique productive TCR sequences. HEC was defined by a CDR3 aa clonotype clonal frequency exceeding 0.1%. Results: Analysis had been made to test the age relationship among a cluster of commonly used immune parameters, such as Shannon’s entropy, clonality and so on. Two outcomes, Shannon index and HEC, had showed a more closed correlation with age. Shannon indexs were significantly decreasing with age (p = 6.2×10-11), while HECs increased with age (p = 5.3×10-10) . Comparison of the peripheral blood T cell repertoire diversity between male and female, we found TCRβdiversity decreases more rapidly in 20 to 40 years for males than for females. No gender difference was observed in the youngest cohort and the oldest age cohort. Lung cancer patients has a lower T cell diversity compared with health people aged 40 years or more (6.43±1.30 vs 6.71±1.70, p = 6.3×10-5). Conclusions: Our data suggest that the human peripheral blood TCR repertoire diversity decrease from young ( < 20 years) to middle-aged ( 20 to 65 years ) to elderly adults ( > 65 years). Moreover, TCR repertoire displays significant gender difference in the 20-40 years age group. Lung cancer patients suffer a poorer immune state than healthy people.
Carcinomas in the children and young adults: A report form Children’s Oncology Group APEC14B1 study.
Authors: Venkatramani Rajkumar , Piao Jin , Krailo Mark D. , Rodriguez-Galindo Carlos , Pashankar Farzana D. 
Published: March 2020

e21505 Background: Carcinomas are rare in the children and young adults. Systematic study of epidemiology and biology of carcinomas in this age group is lacking. Project:EveryChild, A Registry, Eligibility Screening, Biology and Outcome Study (APEC14B1) aims to collect demographic and epidemiologic information of every child and young adult diagnosed with cancer in Children’s Oncology Group institutions. It also serves as a biobank for tumor and biological tissue collected from cancer patients and their parents. Methods: We analyzed the clinical and demographic characteristics of patients with the following diagnosis enrolled in the APEC14B1 study: Thyroid cancer, adrenocortical cancer, colorectal cancer, nasopharyngeal carcinoma, and any other carcinoma. Patients with renal cell carcinoma were not included. Results: Between December 2015 and October 2018, 120 patients with carcinomas were enrolled; thyroid (n = 42, 35.0%), nasopharyngeal (n = 22, 18.3%), colorectal (n = 7, 5.8%), adrenocortical (n = 3, 2.5 %), and others (n = 46, 38.3%). Majority were female (n = 74, 61.7%), mainly due to female predominance (31/42, 73.8%) in thyroid cancer. Majority were white race (n = 81, 67.5 %) and not Hispanic (n = 89, 74.2%). Two patients were enrolled in 2015, 24 in 2016, 47 in 2017, and 47 in 2018. The median age at diagnosis was 15.6 years (range 0.5- 24.6 years). Lymph node involvement was reported in 92 patients and was positive in 58 (63.0%). Metastasis status was reported in 108 and 29 (26.8%) patients had distant metastases. Seventy eight percent (n = 94) of patients agreed to banking of biological material for future research and 90% agreed to be contacted in future for other research studies. Biological samples were banked from 46 patients (48.9%) including tissue submissions from 39 patients, blood submissions from 21 patients and serum submissions from 5 patients. Conclusions: APEC14B1 study was successful in enrolling a large number of children and young adults with carcinomas in a short period of time. Lymph node and distant metastases were common in children and young adults with carcinomas. The enrollment of patients with carcinomas will likely accelerate in the coming years as more institutions open the study. This study will serve as an important resource for investigators interested in clinical and biological research of carcinomas which occur in children and young adults.