bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upstaging the R-ISS classification of newly diagnosed multiple myeloma (NDMM) patients (pts) by quantifying circulating clonal plasma cells (cPCs) via multiparametric flow cytometry (MFC).
Authors: Gonsalves Wilson I. , Jevremovic Dragan , Dispenzieri Angela , Buadi Francis , Dingli David , Lacy Martha , Kapoor Prashant , Lin Yi , Kourelis Taxiarchis , Muchtar Eli , Lust John Anthony , Russell Stephen J. , Go Ronald S. , Hayman Suzanne R. , Leung Nelson , Zeldenrust Steven R. , Kyle Robert A. , Gertz Morie A. , Rajkumar S. Vincent , Kumar Shaji 
Published: March 2020

8031 Background: Our prior studies identified the prognostic significance of ≥400 cPCs/150,000 analyzed events quantified by MFC in NDMM. We evaluated if a similar quantification of cPCs using MFC can add prognostic value to the current R-ISS classification of NDMM pts. Methods: We evaluated all NDMM pts seen at the Mayo Clinic, Rochester from 2009-2017 who had their peripheral blood samples evaluated by 6-color MFC prior to therapy. The cPCs detected were reported as the number of clonal events/150,000 collected total events. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. Results: This cohort consisted of 566 consecutive pts with NDMM with a median age of 66 years (27-95). The distribution of the R-ISS classification of this cohort is as follows: Stage 1- 128 (23%) pts, Stage 2- 369 (65%) pts and Stage 3- 69 (12%) pts. The median number of cPCs was 59 (0-46,412) / 150,000 events. The median time-to-next-treatment (TTNT) and overall survival (OS) for pts with ≥400 cPCs (n = 140, 25%) was 19 months and 46 months compared with 34 months and 77 months for those with < 400 cPCs respectively (n = 426, 75%) (p < 0.001 for both). The median TTNT and OS for pts based on their R-ISS classification as well as with and without the presence of ≥400 cPCs by MFC was as follows in the following Table. Conclusions: Quantifying ≥400 cPCs/150,000 analyzed events by MFC can potentially upstage the R-ISS classification of a subset of NDMM pts with stage I and II disease and identify those pts with a worse than expected survival outcome.[Table: see text]
S1206: A dose-finding study followed by a phase II randomized placebo-controlled trial of chemoradiotherapy (CRT) with or without veliparib in stage III non-small cell lung cancer (NSCLC).
Authors: Argiris Athanassios , Miao Jieling , Cristea Mihaela C. , Chen Allen M. , Sands Jacob , Decker Roy H. , Gettinger Scott N. , Daly Megan Eileen , Faller Bryan A. , Albain Kathy S. , Yanagihara Ronald H. , Garland Linda L. , Byers Lauren Averett , Wang Ding , Koczywas Marianna , Redman Mary Weber , Kelly Karen , Gandara David R. 
Published: March 2020

8523 Background: Veliparib (V), a PARP inhibitor, may potentiate the antitumor effect of CRT in NSCLC. Methods: Eligibility included newly diagnosed unresectable stage III NSCLC. Patients were randomized to receive concurrent CRT with weekly carboplatin (AUC 2) and paclitaxel (45 mg/m2) with V at 120 mg or placebo (P) twice daily during CRT followed by 2 cycles (every 21 days) of consolidation carboplatin (AUC 6), paclitaxel (200 mg/m2) with V at 80 mg or P (per randomized arm) orally on days 1-7 of each cycle. Progression-free survival (PFS) was the primary endpoint. The accrual goal was 132 patients. Results: The dose-finding study results were previously presented (ASCO 2016;A8537). V 120 mg twice daily was the recommended phase II dose. A total of 31 eligible and evaluable patients were enrolled in the phase II randomized trial: 17 on V and 13 on P (1 patient in the V arm withdrew prior to starting any treatment, thus was not evaluable). The study was closed to accrual early due to the positive results from the PACIFIC trial that changed standard practice. Median follow-up among alive patients was 16 months. During CRT, the following grade (G) 3-4 adverse events (AE) were seen with V vs P: any G3 AE (6 vs 6), any G4 AE (2 vs 3), G3 pneumonitis (0 vs 1), G3 esophagitis (1 vs 1), G3 oral mucositis (1 vs 0), G3 anorexia (1 vs 1), G3 hyponatremia (0 vs 3), G3 anemia (1 vs 0), G3 neutropenia (3 vs 1), G3 thrombocytopenia (1 vs 0), G4 hypoglycemia (0 vs 1). Also, 2 patients per arm had G4 lymphopenia. During consolidation (11 evaluable patients with V; 10 with P), G3 anemia (1 vs 0), G3 anorexia (1 vs 0), G3 weight loss (0 vs 1), G3 dehydration (1 vs 0), G3 dysphagia (2 vs 0), G3 fatigue (1 vs 0), G3 hypomagnesemia (0 vs 1), G3 nausea (1 vs 0), G4 hyperglycemia (0 vs 1), G3-4 neutropenia (3 vs 0), G3 thrombocytopenia (1 vs 0), G3-4 lymphopenia (2 vs 1); a G5 pneumonitis occurred in the P arm. Response rates were 56% (95% CI, 31-78%) and 69% (95% CI, 38-91%) on the V and P arms, respectively. PFS at 1 year was 47% (95% CI, 23% - 68%) with V and 46% (95% CI, 19% - 70%) with P. Overall survival (OS) at 1 year was 89% (95% CI, 61%-97%) with V and 54% (95% CI, 25%-76%) with P. Adding the 6 patients treated at 120 mg in the phase I part, 1-year with V was 91% (95% CI, 69%-98%). Conclusions: V in combination with CRT was tolerable with expected toxicities that relate to the backbone regimen. In the small number of randomized patients there was a suggestion of promising survival with V that may provide rationale for future trials of PARP inhibitors with CRT. Clinical trial information: NCT01386385.
Oncologic outcomes of segmentectomy versus lobectomy for radiologically aggressive small-sized lung cancer.
Authors: Kamigaichi Atsushi , Tsutani Yasuhiro , Mimae Takahiro , Miyata Yoshihiro , Imai Kentaro , Ito Hiroyuki , Nakayama Haruhiko , Ikeda Norihiko , Okada Morihito 
Published: March 2020

8525 Background: Despite increasing evidence of favorable outcomes after segmentectomy for indolent lung cancer, such as ground glass opacity-dominant tumors, the adaptation of segmentectomy for radiologically aggressive lung cancer remains controversial. We attempted to elucidate oncologic outcomes after segmentectomy for radiologically aggressive lung cancer. Methods: Data from a multicenter database of 1353 patients with completely resected clinical Stage IA1–IA2 lung cancer at three institutions were retrospectively analyzed to identify radiologically aggressive lung cancer and compare outcomes of segmentectomy versus lobectomy in patients with radiologically aggressive lung cancer using propensity score matching. Results: Multivariable analysis showed that consolidation to maximum tumor (C/T) ratio on preoperative high-resolution computed tomography ( P= 0.037) and maximum standardized uptake value (SUVmax) on 18-fluorodeoxyglucose positron emission tomography/computed tomography ( P= 0.029) were independent predictors of recurrence-free survival (RFS). The criteria for radiologically aggressive lung cancer were determined as C/T ratio ≥ 0.8 or SUVmax ≥ 2.5, for which 522 patients were identified. RFS and overall survival (OS) were significantly worse in patients with aggressive lung cancer (5-year RFS, 83.3%; 5-year OS, 89.4%) than in those without the same (5-year RFS, 97.0%; P< 0.0001; 5-year OS, 97.3%; P< 0.0001). Among patients with aggressive lung cancer, no significant difference in RFS and OS was found between those undergoing lobectomy (n = 392) (5-year RFS, 81.3%; 5-year OS, 88.3%) and segmentectomy (n = 130) (5-year RFS, 90.0%; P= 0.33; 5-year OS, 92.3%; P= 0.76). Among the 111 pairs propensity matched for age, sex, smoking history, solid tumor size, C/T ratio, SUVmax, tumor location, clinical stage, and histology, similar RFS and OS were found between those undergoing lobectomy (5-year RFS, 83.3%; 5-year OS, 88.3%) and segmentectomy (5-year RFS, 90.9%; P= 0.92; 5-year OS, 94.5%). Conclusions: For radiologically aggressive small-sized lung cancer, oncologic outcomes of segmentectomy were equivalent to those of lobectomy.
Identifying actionable somatic mutations in lung cancer using cell-free DNA from bronchial washing fluid.
Authors: Zhang Xin , Zhang Xinyu , Wang Weiran , Huang Jian'An , Zhou Min , Li Chun , Ye Maosong , Zhao Yancheng , Gong Yuhua , Xu Yaping , Hu Qin , Guan Yanfang , Yang Ling , Xia Xuefeng , Zhang Hua , Ren Tao , Shen Qian , Wang Kai , Hou YY , Yi Xin 
Published: March 2020

8528 Background: Bronchial washing is the most common technique for sampling the components of the alveolar space. Here, we evaluated the potential use of bronchial washing fluid (BWF) in liquid biopsy in lung cancer. Methods: This study enrolled 65 lung cancer patients. BWF (separated supernatant and precipitate) samples, peripheral blood lymphocytes (PBL) and formalin-fixed paraffin-embedded tissues were obtained and subjected to next-generation sequencing using a 1021-gene panel. Results: Mutations were identified in 58 (89.2%) of BWF precipitate (BWFp) samples and 64 (98.5%) of BWF supernatant (BWFs) samples, comparing with 61 (93.8%) of tumor tissues. In total, 461 somatic mutations were identified in tissues, of which 331 (71.8%) and 381 (82.6%) were detected in the matched BWFp and BWFs samples. In addition, there were 44.6% of patients carrying actionable variants identified in tissue DNA, including EGFR, ALK, ROS1, RET, etc. (Table). Similarly, there were 40.0% of BWFp samples and 44.6% of BWFs samples identified actionable variants. Moreover, tumor mutation burden (TMB) was also calculated. Nearly 9% of BWFp samples and 23% of BWFs samples were TMB-H (more than 9 mutations per megabase), comparing with 20% of tissues. Significantly, the combined results of three types of samples showed that, 49.2% of patients carrying actionable variants and 24.6% of patients with TMB-H, which suggested more patients benefit from targeted therapy or immunotherapy. Conclusions: In summary, liquid biopsy using BWF showed high potential to identify actionable mutations and to calculate TMB grade of patients with lung cancer, which might be implemented and standardized into clinical use. [Table: see text]
Neutrophil-to-lymphocyte ratio and subsequent recurrence of non-small cell lung cancer patients in remission.
Authors: Chan Abigail Sy , Bentzen Søren , Adashek Michael L , Friedberg Joseph , Culligan Melissa , Khashab Tamara , Miller Kenneth David 
Published: March 2020

8533 Background: Baseline neutrophil-lymphocyte ratio (NLR), a surrogate marker for systemic inflammation and immunosuppression, is a well-established prognostic marker in non-small cell lung cancer (NSCLC). This study tests if interim NLR is prognostic in NSCLC patients in remission. Methods: This single-center, retrospective cohort study analyzed 131 NSCLC patients treated from 2010-2015 who achieved complete remission. Patient data included demographics, histologic subtypes, stage, and treatment type. NLR was calculated at baseline and from the first available blood sample during remission. Kaplan-Meier estimates of overall survival (OS) and time to recurrence were compared using the log-rank test for trend. Multivariable analysis was conducted using the Cox proportional hazards model. Results: Of 131 cases, 63 had subsequently recurred at the last follow up. Mean age was 64 ± 10 years. Histology: adenocarcinoma (60%), squamous cell (33%), and unspecified (7%). Ninety percent were smokers. Thirty-five percent had stage I, 24% had stage II, and 41% had stage III disease. Treatment modalities varied from surgery (28%), chemotherapy (2%), or radiation therapy (10%) alone, or combined (50%). The time from end of treatment, median (range), to the interim NLR was 9.2 months (2.2, 66.7). The baseline and interim median NLR were 2.6 (0.6, 34.0) and 3.1 (0.5, 20.5), respectively. The median follow-up duration was 44 months (5.9, 101). For the univariate analysis interim NLR was binned into tertiles. In multivariable analysis remission NLR remained strongly prognostic for OS (P<0.001) as did patient’s age (P=0.002), but not stage, race, sex, and baseline NLR. Conclusions: Our study found that interim NLR, obtained in remission, was strongly prognostic for OS and recurrence. The results may indicate that even subclinical disease promotes immunosuppression or alternatively that immunosuppression increases recurrence risk. NLR during remission may help identify NSCLC patients at high risk of recurrence and may thus be of value in surveillance of lung cancer survivors. [Table: see text]
Interim safety analysis of consolidation nivolumab and ipilimumab versus nivolumab alone following concurrent chemoradiation for unresectable stage IIIA/IIIB NSCLC: Big Ten Cancer Research Consortium LUN 16-081.
Authors: Yan Melissa , Durm Greg Andrew , Mamdani Hirva , Ganti Apar Kishor , Hrinczenko Borys , Jabbour Salma K. , Feldman Lawrence Eric , Kloecker Goetz H. , Leal Ticiana , Almokadem Salah , Naidoo Jarushka , Fujioka Naomi , Hanna Nasser H. 
Published: March 2020

8535 Background: Consolidation PD-1 inhibition after chemoradiation (chemoRT) for unresectable stage IIIA/IIIB NSCLC improves overall survival. The efficacy and safety of combining a CTLA-4 inhibitor with a PD-1 inhibitor in this setting are unknown but may further improve efficacy in this patient population. Methods: In this randomized, multi-center, phase II study, 105 pts with unresectable stage IIIA/IIIB NSCLC will receive chemoRT, then randomize 1:1 to either nivolumab 480mg IV q4 wks (nivo) or nivolumab 3mg/kg IV q2 wks + ipilimumab 1mg/kg IV q6 wks (nivo/ipi), for up to 24 wks. In this interim analysis, we assess the safety of the first 20 patients treated. Results: From 9/2017 to 11/2018, 20 patients were accrued. Characteristics of those treated on the nivo arm (n = 10) were: median age 62 years, stage IIIA/B 7/3; non-squamous/squamous 7/3; and the nivo/ipi arm (n = 10): median age 61 years; stage IIIA/B 6/4; non-squamous/squamous 7/3. Most toxicities were grade 1 or 2 and the most frequently noted grade 2 AEs included fatigue (25%), pneumonia (25%), extremity pain (20%). Adverse events reported in the Nivo only arm included 81 total events with only four grade 3 events and a single grade 4 thromboembolic event. The Nivo/Ipi arm reported 101 total AEs, with only 3 grade 3 events and a single grade 4 toxicity (amylase elevation). With respect to immune-related adverse events (irAEs), in the nivo arm there were two cases of grade 2 pneumonitis and no grade 3/ 4 events. In the nivo/ipi arm, there was one grade 2 pneumonitis, three grade 3 irAEs (pneumonitis, colitis, pancreatitis), and one asympomatic grade 4 amylase elevation. No treatment-related deaths were observed in either arm. Conclusions: There were no unexpected safety signals in the first 20 patients treated on BIG10CRC LUN 16-081. The incidence of grade 3 or higher irAEs was higher in the nivo/ipi arm, as expected, but this was manageable with the use of established guidelines. The study currently remains open to accrual (32 of 105 have been randomized as of 2/8/19). Clinical trial information: NCT03285321.
The spatiotemporal evolution of early-stage non-small-cell lung cancer.
Authors: Wang Siwei , Zhang Jingyuan , Xu Weizhang , Bao Hua , Fan Xiaojun , Jiang Yunlong , Wu Xue , Wang Xiaonan , Shao Yang , Xu Lin , Yin Rong 
Published: March 2020

8539 Background: Lung cancer is a genetically heterogeneous disease. The genomic basis of tumorigenesis and cancer cell spread, as well as intratumor heterogeneity (ITH) and subclonal evolutionary patterns might correlate with patients’ clinical outcomes. In this prospective study, we aimed to investigate such associations through comprehensive spatiotemporal genomic profiling in early-stage non-small cell lung cancers (NSCLCs). Methods: We performed deep targeted sequencing (GeneseeqPrime, 425 genes) of 503 primary tumor regions and 141 metastatic lymph node tumors from surgery and 378 longitudinal plasma biopsies (pre- and post-operation) across 128 Stage I-III NSCLC patients. ITH and phylogenetic tree for each patient were analyzed and correlated with clinical outcomes. Longitudinal and phylogenetic ctDNA analyses were further performed. Results: Spatial ITH varied among patients and was associated with clinical phenotypes. Geographical stratification of clonal structure, with localized confinement of subclones, was linked with slower tumor progression. In contrast, early expansion of subclones to multiregions was associated with rapid tumor growth and lymph node metastases. EGFR and TP53 mutations were nearly always clonal, whereas subclonal mutations in PI3K, WNT and TGF-beta pathway that occurred later in evolution were found in more than 50% of the patients. By tracking these phylogenetic events, we identified five evolutionary subtypes with distinct clinical outcomes, including a rare subtype characterized by independent origin of multiple EGFR driver mutations. ctDNA profiling could capture the spatial ITH to a certain extent with additional unique signatures. Further longitudinal and phylogenetic ctDNA analyses indicated early detection of relapse and adjuvant chemotherapy resistance. Conclusions: ITH is a key factor associated with clinical outcomes of early-stage NSCLC patients, which show diverse evolutionary subtypes underpinning the disease progression such as lymph metastasis and relapse. ctDNA sequencing can be used to capture spatial ITH, predict recurrence and track drug resistance.
Retrospective study of capecitabine and temozolomide in advanced lung neuroendocrine neoplasms.
Authors: Al-Toubah Taymeyah E. , Morse Brian , Strosberg Jonathan R. 
Published: March 2020

8542 Background: Patients with advanced lung neuroendocrine neoplasms (NENs) have few treatment options. Capecitabine and temozolomide have recently showed significant activity in patients with pancreatic NETs, but data in lung NETs are limited. Methods: We retrospectively reviewed the records of patients treated at a large NET referral center to identify patients seen between 1/2008 and 9/2018 with metastatic lung NENs who received treatment with capecitabine and temozolomide (CAPTEM). Patients who were not seen at the center within the first month of treatment were excluded. Small cell lung cancer patients were also excluded. The primary endpoint was overall response rate per RECIST 1.1. Secondary endpoints included progression free survival, overall survival, and toxicity. Results: 20 patients were identified who received treatment with capecitabine/temozolomide. 14 (70%) were typical lung NETs, 5 (25%) atypical carcinoids, and 1 (5%) was defined as a large cell neuroendocrine carcinoma. 6 patients (30%) exhibited a best response of PR per RECIST 1.1 criteria, 11 (55%) SD, and 2 (10%) PD. 1 patient died 2 months after starting treatment. 11 eventually progressed (radiographically or clinically), only 6 of whom exhibited progression per RECIST 1.1 criteria. Median PFS was 11 months (95% CI, 6 – 16 months). Median OS was 68 months (95% CI, 35 – 101 months). Toxicity profile was mild with mainly grade 1, expected toxicities. 6 patients required dose reduction due to toxicity (2 for diarrhea and nausea, 1 for hand foot syndrome, 3 for thrombocytopenia). Conclusions: We identified a group of patients with metastatic lung NENs who received treatment with the CAPTEM regimen and exhibited a favorable response rate to treatment with a relatively tolerable toxicity profile. This regimen warrants further exploration in a prospective clinical trial.
Lung cancer diagnosed by an incidental lung nodule program or lung cancer screening.
Authors: Smeltzer Matthew , Stevens Walter , Faris Nicholas Ryan , Kethireddy Jennifer , Meadows Meghan Brooke , Ray Meredith , Epperson Amanda , Adams Kim , Fulford Angela , Wagh Ajay , Machin Jim , Tokin Keith , Optican Rob , Wright Jeffrey , Robbins Edward T , Osarogiagbon Raymond U. 
Published: March 2020

8546 Background: Early detection reduces lung cancer (LC) mortality. We prospectively evaluated LC patients diagnosed through Lung Cancer Screening (LCS) or an Incidental Lung Nodule Program (ILNP) (‘early detection’ programs) compared to routinely diagnosed LC patients in a multidisciplinary program (MDP). Methods: We compare demographics, tumor characteristics, and survival between the three groups diagnosed within the same healthcare system from 2015-2018. The ILNP prospectively tracks patients with suspicious lung lesions on routinely-performed studies flagged by radiologists using a standard macro text. LCS used Medicare eligibility criteria. Statistical methods include the chi-square test, Kruskal-Wallis test, and proportional hazards models with hazard ratios (HR) and 95% confidence intervals. Results: ILNP detected 201 lung cancers from 4713 scans (4.3%), LCS yielded 35 lung cancers from 1540 low-dose CT scans (2.3%), while MDC had 926 LC cases not detected by LCS or ILNP. Mean age at diagnosis for ILNP/LCS/MDC was 70/69/67 years (p = 0.0083); African Americans were under-represented in LCS (25%/11%/32%, p = 0.0104). LCS had the highest proportion with commercial insurance (46%/54%/43%, p = 0.3442). Early detection groups were more likely to have adenocarcinoma histology (ILNP/LCS/MDC: 61%/57%/49%, p = 0.0113). Smoking exposure was highest in LCS cohort (mean pack years: 48/64/52, p = 0.0500); 11% of ILNP, 8% MDC patients were never-smokers. Only 36% ILNP and 39% MDC patients were eligible for LCS by NLST criteria and 30%/40% by NELSON criteria. Reasons for ineligibility included smoking status in 73-90% and age in 7-27% of patients. Stage I/II distribution was (66%/58%/21%, p < 0.0001), stage IV 15%/20%/36%; surgical resection rates were (56%/55%/31%, p < 0.0001). Overall survival was longer in early detection groups (LCS HR: 0.31 [0.11,0.82]; ILNP HR: 0.51[0.33,0.81]) compared to MDC (p = 0.0011). Conclusions: The majority of LC patients were ineligible for LCS, but the ILNP identified LC in a high proportion of such patients, with similar stage re-distribution, curative-intent treatment, and survival rates. Structured ILNP complement LCS for early LC detection, such programs need to be built out.