bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health related quality of life (HRQoL) outcomes from the phase III CANDOR study comparing carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in patients (Pts) with relapsed or refractory multiple myeloma.
Authors: Siegel David Samuel DiCapua , Weisel Katja , Zahlten-Kumeli Anita , Medhekar Rohan , Sapra Sandhya , Ding Bifeng , Leleu Xavier 
Published: May 2020

e20563 Background: In the CANDOR study (N = 466) of pts with relapsed or refractory multiple myeloma (RRMM), a statistically significant improvement in progression-free survival (HR = 0.63; 95% CI, 0.46-0.85; p = 0.0014) was observed in the KdD vs Kd arms. Here, we report a secondary endpoint of CANDOR evaluating HRQoL. Methods: HRQoL was assessed using the Global Health status (GHS)/Quality of Life (QoL) domain of the European Organisation for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30), which was completed on Day 1 of Cycle 1 and every 28±7 days through the first follow-up visit. The GHS/QoL was scored from 0–100, with higher scores indicating better QoL. The scores were compared between the KdD and Kd arms using a restricted maximum likelihood-based mixed effects model for repeated measures under the assumption of missing data at random. A minimally important difference of 5 points between arms was prespecified. An exploratory time-by-time sensitivity analysis by ANCOVA was used to evaluate the treatment effect on the GHS/QoL score among pts who remained on treatment until the specified visit (cycle 3 and every 3 cycles thereafter). Results: GHS/QoL completion rates from baseline through up to cycle 26 (study ongoing) for randomized pts who remained on treatment were > 81% for both the KdD and Kd arms; the median extent of missing GHS/QoL data was 5.3% for the KdD arm and 12.1% for the Kd arm. KdD was associated with higher GHS/QoL scores relative to Kd starting at Cycle 7 and this was maintained until Cycle 26 (by mixed effect model, overall LSME difference [95% CI], 0.06 [–2.39, 2.50]; p = 0.96). At Cycle 18, the mean difference between arms approached the prespecified clinically meaningful difference of 5 points (by ANCOVA, [difference: KdD–Kd (SE), 4.06 (2.45)]). In an exploratory analysis of pts who remained on treatment at each cycle, a higher rate of pts reported an improvement of ≥10 points in GHS/QoL score from baseline in the KdD vs Kd arms, with the greatest differences observed at Cycle 7 (Odds Ratio [OR] for KdD/Kd [95% CI], 2.37 [1.29, 4.34]), Cycle 9 (OR [95% CI], 2.96 [1.46–6.03]), Cycle 13 (OR [95% CI], 2.44 (1.15-5.17), and Cycle 16 (OR [95% CI], 2.77 [1.27–6.07]). Conclusions: In addition to the superior clinical benefit observed with KdD vs Kd, HRQoL was maintained with the KdD triplet. A higher rate of pts treated with KdD reported an improvement of ≥10 points from baseline. Clinical trial information: NCT03158688.
HealthTree Patient Portal mediated myeloma patient-reported vaccination and antibiotic use.
Authors: Thompson Michael A. , Ahlstrom Jenny , Sweeney Nathan W. 
Published: May 2020

e20567 Background: Multiple myeloma (MM) is a cancer of the immune system. Infection is a major cause of morbidity and mortality in MM. Vaccines are the first line of prevention for infectious diseases. Anti-microbial prophylaxis may improve patient (pt) outcomes, but real-world use has not been well characterized. In order to engage the pt community regarding vaccination we utilized HealthTree (www.healthtree.org). Methods: An investigator-submitted online survey asking about infection prophylaxis and vaccinations was fielded to 4,944 pts from May 10, 2019, to January 9, 2020. The HealthTree platform queries pts about sharing data for research purposes. De-identified responses were aggregated and reviewed. The study was determined to be exempt by the Western Institutional Review Board. Results: 458 MM pts participated in the surveys and were able to select more than one option with the total response indicated below. Abbreviated questions and simplified responses are noted in Table including: 1. Have you ever been vaccinated in the last 5 years with a pneumococcal vaccine (PV)? 2. In the last 3 flu seasons, have you received the influenza vaccine (FV)? 3. After you began myeloma treatment, did you ever receive the anti-Varicella Zoster Virus (VZV, shingles) vaccine? 4. Were you (or are you currently) treated with anti-viral prophylaxis? 5. Were you (or are you currently) treated with antibiotic bactrim? 6. Were you (or are you currently) treated with levofloxacin prior to stem cell transplant or at the beginning of your MM therapy? Conclusions: Both FV and PV were fairly high in this self-selected cohort of volunteers compared with a large health system ( http://ow.ly/O8Dx30b9Wuc ) and a global registry ( http://ow.ly/Uofg30h6Qen ). Most did not receive an anti-VZV vaccine, but a few received a live vaccine. Anti-viral prophylaxis was common, but not universal. Anti-PJP and levofloxacin use were reported by a minority of participants. Pt reported interventions via an online portal can help investigators survey the pt community and result in hypothesis generating research questions including investigating vaccine: types, dosing, sequencing, and use of anti-infective interventions. [Table: see text]
Impact of doxycycline on outcomes in AL amyloidosis.
Authors: Blue Brandon Jamaal , Duncanson Lauren , Hansen Doris K. , Zhang Yumeng , Liu Hien D , Nishihori Taiga , Ochoa-Bayona Jose L. , Baz Rachid C. 
Published: May 2020

e20568 Background: It has been shown in mouse models doxycycline(Doxy) interferes with amyloid fibril formation. Retrospective data suggests the addition of Doxy to standard chemotherapy(chemo) reduces mortality in cardiac amyloidosis. We examined the relationship between Doxy use, treatment, and OS in a cohort of AL Amyloidosis(AL) within an academic center. Methods: AL pts between 2008 and 2020 at Moffitt Cancer Center. For this study we included patients with AL, with all types of organ involvement. We excluded pts with non-AL Amyloidosis and pts with localized amyloidosis were excluded. Data on organ involved, organ response, date of death, treatment were obtained for each pt. OS was defined as time from AL diagnosis to date of death. Univariate comparisons were performed to identify differences in treatment and other prognostic variables between Doxy groups, where appropriate (Table). Results: 209 pts that met inclusion criteria, 13 pts(6%) had cardiac involvement with AL. Of those 13 pts, only 3 pts(23%) received Doxy in addition to standard of care chemo. For this study, we included all types of AL for total 209 pts. Of the 209 pts, 9.5% received Doxy in addition to standard of care chemo and 90.5% pts did not receive Doxy and had chemo alone. Pts who received Doxy had more proteinuria (suggesting more significant renal involvement) but other characteristics were not statistically different including cardiac biomarkers (table). A numerically higher rate of organ response (67% versus 43%) was noted in patients who received Doxy but this didn’t reach statistical significance. Further the OS was numerically higher for Doxy treated pts however again this didn’t meet statistical significance. Conclusions: We noted higher organ responses and overall survival in Doxy treated pts, we could not identify statistical differences in outcomes possibly because of the sample size. Nevertheless, further follow up is warranted and Doxy may be associated with improved outcomes in AL. [Table: see text]
Comprehensive analysis of T-cell receptor sequencing in resectable squamous cell lung cancer patients with neoadjuvant therapy of PD-1 inhibitor and chemotherapy.
Authors: Feng Yuan , Xiao Shanshan , Sun Wei , Ma Yuanyuan , Hong Yang , Pu Yue , Lin Rui , Wang Tao , Lin Dongmei , Yang Yue 
Published: May 2020

e21012 Background: Cancer therapies alter the tumor microenvironment such as the infiltration of T cells. Neoadjuvant therapy to squamous cell lung cancer patients using PD-1 inhibitor expands specific T cell clones. However, the T cell clones and diversity in tumors and lymph nodes according to different neoadjuvant settings remain largely unknown. In this study, we used T-cell receptor (TCR) sequencing technology to investigate the TCR clonotypes and diversities in squamous cell NSCLC patients who received neoadjuvant chemotherapy and PD-1 inhibitor plus chemotherapy. Methods: Tumor tissues, non-metastatic lymph nodes (NMLN)s, and available metastatic lymph nodes (MLNs) were collected from two patient groups. Each group enrolled three patients who received either neoadjuvant chemotherapy or PD-1 inhibitor plus chemotherapy. DNA samples were harvested and processed for multiplex PCR for the third complementary determining region (CDR3) of TCR-β chain followed by the next generation sequencing analysis. Differences of the CDR3 clonotypes and clonal diversities were analyzed by bioinformatics tools including the Mixcr software. Results: For all the six patients, TCR clonotypes in the tumor tissues were found to be fewer than those from the lymph nodes in the same patient, consistent with a hypothesis that most of the tumor infiltrated T cells after therapy derive from the lymph nodes. Some clonotypes among the top 10 highest frequencies were found in different samples from the same patient, further supporting the lymph node origin of the tumor infiltrating T cells after therapies. Interestingly, TCR clonal diversity was higher in the NMLNs compared with the MLNs, but clonotype overlap with tumor tissues was higher in the MLNs than NMLNs; these results could imply that TCR clonotypes in the primary lymph node were more stimulated. Additionally, there were very few clonotypes shared between different patients, indicating the heterogeneity of immune response for different individuals. Due to the limited sample size, we could not find the systemic difference between the two patient groups. Conclusions: TCR sequencing technology can detect the CDR3 clonotypes in tumor tissues and lymph nodes of cancer patients, providing new opportunities for revealing patients' response to chemotherapy and immunotherapy. Further analysis will be performed to investigate TCR clonotype differences caused by immunotherapy.
The mutation profile of genes related to primary resistance to EGFR-TKI in early NSCLC.
Authors: Ye Jiangang , Zhang Qi , Zhang Xing , Qin Huijuan , Tian Minqi 
Published: May 2020

e21014 Background: In targeted therapy for patients with advanced non-small cell lung cancer (NSCLC), approximately 30% of NSCLC patients with EGFR mutations develop primary resistance at the beginning of treatment with TKIs. However, the knowledge of primary resistance in early-stage NSCLC patients with EGFR positve remains poorly understood. Methods: Mutations of nine genes that may be related to primary resistance EGFR TKIs in advanced non-small cell lung cancer were chosen through pubmed and other databases including EGFR T790M, EGFR 20ins, PIK3CA, KRAS, BRAF, ERBB2 amplification, MET amplification, PTEN deletion and BCL2L11 deletion. Gene mutations related to primary resistance in patients with early-stage lung cancer (I-IIIA) from the TCGA database were analyzed. Results: According to TCGA database, there were 1089 patients with NSCLC of which 585 were lung adenocarcinoma and 504 lung were squamous cell carcinoma. A number of 46 EGFR-sensitive (19del / L858R) mutations were observed in adenocarcinoma, of which the clinical information of which 44 cases harbored competed clinical information including 39 patients with early stage could be identified as follows,1 patient in stage I, 11 patients in stage IA, 8 patients in stage IB, 7 patients in stage IIA, 4 patients in stage IIB, 8 patients in stage IIIA, 1 patient in stage IIIB and 4 patients in stage IV, respectively. Among the 39 cases of early non-small cell lung cancer with EGFR-sensitive mutations, 2 case of EGFR T790M mutations (5.12%), 2 case of PIK3CA (5.12%), 2 case of BRAF (5.12%), 11 case of MET (DUP) (28.2 %), 8 case of ERBB2 (DUP) (20.5%) and 5 case of PTEN (Del) (12.8%) mutations were observed respectively. Meanwhile, none of primary resistance gene mutations could be found in non-small cell lung squamous cell cancer(0/1). Conclusions: The presence of different mutation frequency in the primary resistance genes associated with EGFR TKIs in patients with early NSCLC was proved. Our study suggested it was necessary for patients to test mutations in primary resistance genes before accepted the adjuvant and neoadjuvant therapy using TKIs. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.
Phase I/II study of vorolanib plus nivolumab in patients with thoracic malignancies: immunotherapy (IO) correlatives to differentiate responders from nonresponders.
Authors: Beckermann Katy , Bestvina Christine M. , Whisenant Jennifer G. , Borghaei Hossein , Owonikoko Taofeek Kunle , Berry Lynne D , Shyr Yu , Liang Chris , Selvaggi Giovanni , Wakelee Heather A. , Horn Leora 
Published: May 2020

e21019 Background: VEGF inhibition is suggested to enhance innate T cell function, activate dendritic cells, block recruitment of regulatory T cells, and decrease myeloid-derived suppressor cells. Vorolanib is a tyrosine kinase inhibitor that is structurally similar to sunitinib but designed to improve safety without compromising efficacy. Response to checkpoint inhibitors in patients with thoracic tumors is limited, thus we designed this multi-institutional, phase I/II study (NCT03583086) to explore safety and efficacy of combining vorolanib and nivolumab. Here we present updated results in the NSCLC, thymic, and SCLC cohorts, including patients previously treated with single agent IO. Methods: The Phase I maximum tolerated dose was 200 mg vorolanib and 240 mg nivolumab q2w. Phase II is ongoing and uses a two-stage MinMax design to assess the objective response rate (RR) in SCLC, thymic carcinoma, and three NSCLC cohorts: 1) IO naïve; 2) primary refractory, defined as radiographic progression < 12 weeks of starting IO; and 3) acquired resistance, defined as achieving at least stable disease ≥12 weeks to IO followed by progression. Results: As of December 2019, 37 patients had enrolled, 38% female, 11% never smokers, median age 66. The disease control rate (DCR) across all cohorts is 65% (20/31 evaluable patients) and the RR is 13% (4/31). In the NSCLC cohort, the overall RR is 14% (3/21); the RR is 33% (2/6) in IO naïve patients, including 2 on therapy > 17 months. RR in the NSCLC patients with acquired resistance is 14% (1/7) with an 86% (6/7) DCR. No responses in the primary refractory cohort but the DCR is 50% (4/8). DCR in the SCLC and thymic cohorts is 40% (2/5) and 50% (2/4), respectively; 1 thymic patient had a partial response with a complete response in target lesions. Exploratory correlatives, including mass cytometry analysis and single cell gene expression, are being performed in order to understand changes in macrophages and T cell activation markers to differentiate the underlying biology of the tumor and the microenvironment between responders and nonresponders. Conclusions: The addition of vorolanib nearly doubled the RR in the IO naïve NSCLC patients compared to historical data with single agent nivolumab. Additionally, 67% of NSCLC patients with prior IO achieved at least stable disease, 1 patient with acquired resistance had a response. Correlatives that may help define biomarkers of response to therapy will be presented among different cohorts of patients. Clinical trial information: NCT03583086 .
Clinical and patho-genomic characteristics of concomitant mutated status of TP53, EGFR, KRAS genes in Chinese patients with resected lung adenocarcinoma.
Authors: Yuan Qiu , Yang Haihong , Chen Hanzhang , Deng Qiuhua , Liu Liping , Xiao Dakai , Lin Yongping , He Jianxing , Zhu Changbin , Li Weiwei , Shao Di , Jiang Wenxi 
Published: May 2020

e21024 Background: Alterations of TP53, EGFR, KRAS genes are of importance in LUAD etiology, vital prognostic markers as well as therapeutic targets as recently reported. In addition, in advanced or metastatic NSCLC, concomitant mutations of TP53 with EGFR or KRAS closely associated with prognosis and TKIs’ efficacy. While, distribution of concomitant mutations of TP53, EGFR and KRAS in early stage or resectable LUAD remained to be elucidated. Methods: 434 patients with defined pathological diagnosis of LUAD were recruited from 1st.Jan.2019-31st.Dec.2019, which made 468 FFPE blocks for the study. Histology and composition were given by authorized by pathologist. Genomic DNA from FFPE samples and peripheral blood was extracted. 636 cancer-related genes were specifically captured and sequenced by MGI-seq 2000. Association of concomitant status with clinical and genomic characteristics was further analyzed. Results: Generally, TP53, EGFR and KRAS mutation rate is 26.7%, 60.9% and 10% respectively. Among these samples, Subtypes of EGFR mutations significantly differed in between tumors rising in left and right lung (P = 0.048). Tumors with KRAS mutations occurred more easily in right lung than those with TP53 or EGFR mutations (P = 0.012, P = 0.043 respectively). In addition, histology subtype and clinical stage were closely associated with TP53, EGFR and KRAS mutation status (P < 0.001). 90 samples (19.2%) carried concomitant TP53 and EGFR mutation, 14 samples (3%) were TP53/KRAS co-mutated. LUAD samples with EGFR amplification had higher rate of concomitant TP53/EGFR mutations (RR:1.1,95%CI: 1.032 to 1.159,P = 0.0009). Moreover, KRAS G13 mutated samples more easily co-mutated with TP53 mutations compared with those with mutations in G12 loci (RR:1.33,95%CI: 1.24 to 1.37,P = 0.024). Further, samples with non-concomitant TP53 mutations had highest level of tumor mutation burden (muts/Mb) (median TMB = 9.74 vs 2.05 for TP53/EGFR/KRAS wild type, P < 0.0001). Samples with concomitant TP53/EGFR mutations and TP53/KRAS mutations displayed higher TMB level than their non-concomitant compartment (P < 0.001 and P = 0.05 respectively). Conclusions: TP53,EGFR and KRAS mutations and their concomitant mutation status displayed diverse correlation with spatial, clinical and genomic characteristics in resectable LUAD patients. This correlation may indicate complex biological heterogeneity of LUAD which may need further exploration.
The validity of 5-aminorevrinic acid as a biomarker for risk screening and supportive diagnostic parameters in lung cancer patients.
Authors: Yamauchi Yoshikane , Saito Yuichi , Murakami Koji , Kanamoto Yasuyuki , Asami Momoko , Yokote Fumi , Sakai Takashi , Sakao Yukinori , Tanaka Toru , Kawamura Masafumi 
Published: May 2020

e21027 Background: Early detection and treatment of cancer is an important issue that affect the prognosis of cancer patients. Photodynamic screening with 5-aminorevrinic acid (ALA-PDS) is simple and non-invasive procedure for risk screening of cancer, and it is gradually recognized as the predictable biomarkers for cancer in Japan. In this study, we examined the predictability of lung cancer by ALA-PDS and its usefulness as a supportive parameter for preoperative diagnosis. Methods: Eighty-five lung cancer patients (48 males and 37 females) just before lung resection were enrolled. 5-aminolevulinic acid phosphate 150mg was taken at night and urine samples were collected in the next morning. The porphyrin metabolites in the urine samples were detected by solid phase extraction method, previously reported from our group. Afterwards, the data was adjusted depending renal function. The data was compared with that from healthy volunteer without any abnormal symptom and physical disorder. Results: The average age of 85 patients was 70 years (46-85). The number of patients in each pathological stage was 2 in Stage 0, 58 in Stage IA and IB, 15 in Stage IIA and IIB, 8 in Stage IIIA and IIIB, and 2 in Stage IV, respectively. The diagnosis was 61 cases of adenocarcinoma and 22 cases of squamous cell carcinoma. Urinary porphyrin metabolites in lung cancer patients increased significantly as compared to those of healthy volunteers (2,847nM/gCRE vs 1,668nM/gCRE, p < 0.001). Increase of urinary porphyrin metabolites was observed even in stage 0 or I patients, but the correlation with stage progression was not clear (Stage 0 and I vs Stage II vs Stage III and IV: 2,757nM/gCRE vs 3,099nM/gCRE vs 3,010nM/gCRE). Furthermore, urinary porphyrin metabolites were confirmed to be significantly increased even in PET-negative cancer patients, compared to healthy volunteers (p < 0.001). Conclusions: ALA-PDS was able to predict lung cancer in our cohort. Moreover, it was also suggested that it may be useful as a supportive parameter for diagnosis of early stage lung cancer or PET negative lung cancer.
A rare family case study of multiple siblings with multiple synchronous primary lung cancers.
Authors: Lin Rui , Wang Tao , Xiao Shanshan , Mao Ruifang , Pu Yue , Liu Hong 
Published: May 2020

e21028 Background: Familial lung cancer is rare, let alone inherited lung cancer with multiple synchronous primary lung cancer lesions. Study of inherited lung cancer may facilitate the understanding of the molecular mechanism of the tumorigenesis. Methods: We identified an extremely rare family of five siblings, four with multiple primary lung adenocarcinomas by pathological examination. DNA samples were extracted from the patient tumor tissues and libraries were prepared for next-generation sequencing (NGS) analysis using a custom 500-gene cancer panel. Results: EGFR L858R or 19DEL mutations were identified in at least one lesion in all of the four lung cancer patients. Interestingly, lung cancer patient L1 had EGFR 19DEL in one lesion and L858R in the other, lung cancer patient L2 had EGFR L858R and KRAS G12C mutation in lesion 1 and lesion 2, respectively. The mutation statuses of EGFR and KRAS were confirmed by ARMS-PCR. The mutational spectrum of the two lesions from the same patient distinguished significantly based on the 500-gene NGS panel analysis, further demonstrating the heterogeneity of cancer mutations. Taken together, these results indicate that patients L1 and L2 both had synchronous primary lung cancers. Due to the small lesions, the two lesions for patient L3 were mixed together; the concurrent EGFR L858R and 19DEL mutations in the tissue sample implicated different drivers in the two different lesions since co-occurring of these two mutations was very rare. For patient L4, EGFR L858R was identified in one lesion and uncommon mutations with low frequencies were observed in the other lesion, consistent with different driving mechanisms for the two lesions. Conclusions: To our knowledge, this is the first study identifying a family of multiple siblings with multiple synchronous primary lung cancers and using NGS to reveal the genetics. Together with germline mutation analysis, this study may shed light on the tumorigenesis of familial lung cancer.