bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venetoclax induces sustained complete responses in refractory/relapsed patients with cardiac AL amyloidosis.
Authors: Le Bras Fabien , Dupuis Jehan , Lemonnier François , Oghina Silvia , Bodez Diane , Ladaique Amandine , Maarek Alizee , Roulin Louise , Beldi Ferichou Asma , Frenkel Valerie , Haioun Corinne , Damy Thibaud , Belhadj Karim 
Published: March 2020

e19538 Background: Venetoclax (VEN) is an orally bioavailable small molecule inhibitor of the anti-apoptotic protein BCL-2 and has been shown to have efficacy against myeloma (MM), particularly in patients that harbor t(11;14). Approximately, 50% of AL amyloidosis patients will exhibit t(11;14) making VEN an attractive therapeutic option. Methods: We here report the results of a retrospective analysis of a monocentric series of refractory/relapsed (R/R) patients (pts) heavily pretreated with cardiac AL amyloidosis treated in a french academic center. VEN was given daily alone or in association with dexamethasone (DEX), with or without bortezomib (BTZ). Treatment was planned to be administered until progression. Results: Between February 2017 and January 2019, 7 consecutive R/R pts have been treated. All had received previous BTZ and daratumumab (DARA) containing regimen. Baseline characteristics were: median age: 72.7 years (range 40-84), Mayo Clinic stage: stage I in 2 pts, stage II in 3 and stage IIIA in 2. All patients but one had in addition to cardiac deposit, systemic involvement including kidney, joint, neurologic, gastro-intestinal tract, lymph node and muscle. All but one pts were refractory to their last treatment consisting of DARA-DEX with or without IMID. The t(11;14) translocation was present in 5 pts, absent in 1 and undetermined in 1 pts. Two pts had concomitant MM at diagnosis. Median number of previous line treatments was 4 (3-5). Five patients received VEN- BTZ- DEX as described in MM (PMID: 28847998), 1 with DEX and 1 as monotherapy. Five pts received 400 mg/d, one 200 mg/d and one 100 mg/d. Median duration of treatment was 76 days (30-713). All patients but one are still on treatment. One patient treated with 400 mg/d had a dose reduction to 100 mg/d due to grade 2 diarrhea. Four patients received at least 2 cycles and were evaluable for response. One 84 y old patient in stable disease after 1 cycle died due to influenza infection. 2 patients received only one cycle of treatment. Hematological complete response occurred in 2/4 (50%) patients, after 63 and 27 days. Interestingly, responses were sustained as the 2 responders were still on therapy after 76 and 713 days. This later patient, refractory to 2 previous lines had a cardiac and neurologic response. The 2 responding patients had proven t(11:14). Conclusions: On this limited series of heavily pretreated patients with R/R AL cardiac amyloidosis VEN used as a single agent or in combination can induce prolonged response and seems a promising drug with an acceptable safety profile in patients with t(11;14).
LUNG cancer in Lleida: An epidemiologic study.
Authors: Cordoba Juan Felipe , Morales Serafin , Adaniel Christina , Veas Rodriguez Joel , Rodriguez Galindo Álvaro , Salud Antonia 
Published: March 2020

e20003 Background: According to GLOBOCAN, in 2018 lung cancer was associated with the greatest incidence and mortality attributable to cancer worldwide: 27.9 cases/100,000 habitants and 23.5 cases/100,000 habitants, respectively. In Spain, lung cancer is the fourth most frequent cancer but the first cause of cancer mortality in the country. We have undertaken this study to compare the epidemiologic data for lung cancer in our Spanish provincial population with those worldwide and nationwide. Methods: This was an observational, retrospective study. It included all patients with lung cancer in the Lleida province of Catalonia, Spain in a period of 6 years, from January 2011 to December 2016. Data taken from electronic medical records included variables such as sex, age of diagnosis, smoking history, histology, stage, and oncologic treatments, among others. Incidence, prevalence, survival and mortality rates were determined, as well as the main clinical characteristics of the cohort. Results: Seven hundred eighty-two patients with a diagnosis of lung cancer between January 2011 and December 2016 were included. Median follow-up was 11.7 months. Men comprised 78.6% of the cohort. The median age at diagnosis was 66.6 years. More than half of the patients (53.2%) smoked at the time of diagnosis. The majority were adenocarcinomas (44.1%), with 33.2% squamous cell carcinomas, and 12.1% small cell carcinomas. EGFR testing was performed in 300 patients. 18.7% were positive for a mutation, of which 69.7% were exon 19 insertions. At diagnosis, 52.3% of cases were stage IV, 25.3% stage III, 7.3% stage II, and 14.5% stage I. The average annual incidence rate was 37 cases/100,000 habitants. The median overall survival (OS) was 12.3 months (95% CI: 10.7-13.8). The OS at 1 year was 50.8% (95% CI: 47.3-54.3) and at 5 years was 13.7% (95% CI: 10.2-17.2). The estimated mortality rates were 49.2% in the first year and 86.3% at 5 years. Conclusions: In the Lleida province of Spain, the incidence and mortality associated with lung cancer are greater than global rates but lower than those of Spain as a whole (incidence: 37 vs 58 cases/100.000 hab). Lung cancer survival at 5 years is greater than countrywide statistics (12,3% vs 9.9 %). The heathier lifestyle and rural geography may favor the lower incidence of lung cancer in Lleida compared with the rest of Spain.
Blood-based TMB detection and dynamic monitor in local advanced non-small cell lung cancer (NSCLC) patients.
Authors: Yang Xi , Zhu Zhengfei 
Published: March 2020

e20039 Background: TMB detection has been recommended by NCCN guidelines as an effective biomarker for immunotherapy of advanced non-small cell lung cancer(NSCLC). Blood based TMB(b-TMB) detection is considered to be able to predict the efficacy of immunotherapy in patients with advanced NSCLC. Concurrent chemoradiotherapy is the standard treatment for locally advanced NSCLC(LA-NSCLC) and subsequent consolidated immunotherapy has become the standard treatment. Therefore, the b-TMB status and dynamic changes in patients with LA-NSCLC are particularly important. Methods: We enrolled 7 patients with LA-NSCLC, each receiving 60Gy chest radiotherapy and docetaxel plus cisplatin weekly regimen chemotherapy. We tested the TMB by next-generation sequencing with 520 genes panal in tissues and blood of each patient at baseline. In addition, b-TMB was measured dynamically in 6 patients at different time points during chemoradiotherapy, each two patients were tested for over four times within one week of treatment, two weeks later and four weeks later. Results: As shown in the table, the baseline b-TMB matched the tissue TMB. Except for one ALK fusion patient, the positive rate of b-TMB was 100% and the Spearman correlation value was 0.899(p = 0.015). B-TMB fluctuated but did not change much within first two weeks of concurrent chemoradiotherapy. After the fourth week of chemoradiotherapy, b-TMB significantly decreased in all patient. Conclusions: In patients with LA-NSCLC, b-TMB is a reliable biomarker, which is likely to change in the later stage of concurrent chemoradiotherapy. Its dynamic monitor will help to distinguish which patients may benefit from consolidated immunotherapy after concurrent chemoradiotherapy. [Table: see text]
Impact of invasive regional lymph node examination (IRLNE) and time to radiation on overall survival for patients with stage I NSCLC treated with SBRT- a NCDB analysis.
Authors: Patil Pradnya Dinkar , Wei Wei (Auston) , Pennell Nathan A. 
Published: March 2020

e20041 Background: SBRT is the standard of care for patients (pts) with early stage NSCLC who are not surgical candidates due to co-morbidities. Current NCCN guidelines state that IRLNE prior to definitive treatment for stage IA NSCLC is optional. Performing SBRT without IRLNE may increase the risk for occult nodal metastasis that could lead to regional recurrences and impact survival, however small retrospective studies have failed to demonstrate any benefit of IRLNE. Prior studies have also shown that delay in time to surgery impacts survival in stage 1 NSCLC pts, and due to co-morbidities SBRT pts are more likely to have a delayed time to radiation. However, the impact of time to radiation on OS in such pts is not well defined. Methods: We queried the NCDB for pts with stage 1 NSCLC treated with SBRT diagnosed from 2004 to 2014. We identified whether regional lymph nodes were examined for these pts. In addition, we obtained data regarding other clinicopathologic and treatment associated variables. Kaplan Meier method was used for survival analysis. Cox proportional hazards model was used to assess the impact of the co-variates on OS. Results: We identified 15,338 pts with stage 1 NSCLC treated with SBRT. Of these, 943 pts had IRLNE. Median age was 75 years (range 26-90) and Charlson-Deyo score was ≥ 1 in 6,427 pts. Median OS was 35.4 months (95% CI 34.6-36.2 months). The median time to radiation from diagnosis was 57 days. In a multivariate analysis, there was no impact of IRLNE on OS. Other clinicopathologic variables that impacted OS are listed in the table. A delay in initiation of radiation was associated with significantly worse OS. Conclusions: Invasive staging prior to SBRT for stage I NSCLC does not impact OS. A delay in initiating definitive radiation adversely affects survival in this population and the risk is incremental per week delay. [Table: see text]
Clinical and prognostic implications of sarcopenia in patients affected by locally advanced NSCLC.
Authors: Rossi Sabrina , Disconzi Luca , Toschi Luca , Finocchiaro Giovanna , Giordano Laura , Lanza Ezio , Lutman Romano Fabio , Santoro Armando 
Published: March 2020

e20046 Background: Sarcopenia is a loss of skeletal muscle mass that has been studied as prognostic factor in several cancers. Retrospective studies have suggested that sarcopenia is associated with poorer survival outcomes and with an increase of major chemotherapy toxicities resulting in dose reduction and delay. This study examined the value of sarcopenia in patients with stage III non-small cell lung cancer (NSCLC). Methods: This retrospective analysis includes 68 patients affected by stage III NSCLC treated with induction chemotherapy followed by surgery or radical radiation therapy in our cancer center. Weight and height were obtained from medical records at diagnosis. Skeletal muscle index (SMI) was measured by the analysis of electronically stored computed tomography images obtained before the start of chemotherapy; sarcopenia was defined by international consensus as a SMI≤39 cm2/m2 for women and ≤55 cm2/m2 for men. Kaplan-Meier method and Log-Rank test were used to determine the impact of sarcopenia on overall survival (OS) and progression-free survival (PFS). Exact Fisher test and Chi-squared test were used to establish the association between the presence of sarcopenia and other variables. Results: A total of 68 patients (stage 3A = 39; stage 3B = 29) with performance status 0-1 and median age 67 yrs were analyzed. Forty-five patients (66%) were sarcopenic: 100% of underweight patients (BMI ≤18.5), 83% of patients with normal weight (BMI 18.5-24.9), 56% of overweight patients (BMI 25-29.9) and 30% of obese (BMI≥30). Sarcopenia was not associated with age≥70 yrs (p = 0.67), Charlson Comorbidity Index (p = 1.00), stage (p = 0.53), response rate to chemotherapy (p = 0.78) or toxicities of grade≥3 (p = 0.83). Median OS in sarcopenic patients was 18.2 months compared with 33.2 months in nonsarcopenic patients (p = 0.03); the difference in terms of PFS was not statistically significant (10.7 vs 14.9 months; p = 0.19). Conclusions: Sarcopenia is associated with shorter OS in patients with locally advanced NSCLC but it seems not related with worse response to induction chemotherapy or higher toxicities. These data should be validated in larger prospective clinical studies.
Mutation concordance of matched tissue sample and blood sample: A result of 456 lung cancer patients.
Authors: Wen Xiaoping , Bin He , Lei Ye , Jing Zhang , Li Lifeng , Peisu Suo , Song Lele , Chen Shifu , Jianhua Chen 
Published: March 2020

e20049 Background: Cell-free DNA (cfDNA) sequencing is an important alternative for tissue sequencing when tissue samples are not available. To better study the association of a blood sample and tissue sample, we designed a study to evaluate the concordance of gene mutations of tumor tissues and matched cfDNA. Methods: From May 2017 to January 2019, 456 lung cancer patients were enrolled in this study. For each patient, a matched tumor tissue sample and blood sample were collected. DNA samples were extracted from these samples, and then sequenced with a pan-cancer gene panel. Results: The concordance ratio was computed by the number of common variants divided by the summation of common variants, the number of tissue-specific variants and number of blood-specific variants. Among these 456 patients, an overall by-variant concordance ratio of 49.7% (1457/2932) was observed. When considering only the major driver genes, the observed concordance ratios were EGFR = 45.7% (96/210), KRAS = 48.5% (147/303), ALK-fusion = 50% (8/16) and BRAF = 52.5% (21/40). The mean variant allele frequency (VAF) of common variants was significantly higher than the mean VAF of variants only detected in tissue (29.07% vs. 12.29%, p-value < 2.2e-16). Conclusions: This study shows that the concordance ratio between a tissue sample and a blood sample is close to 50%. As new technologies are being developed to detect low-frequency variants better, we can expect this concordance ratio to improve in the future.
Characterizing biomarker testing over time in lung cancer patients using oncology electronic medical records (EMR).
Authors: Christian Jennifer , Wagner Joe , Mastrogiovanni Gregory , Norden Andrew David , Kurashige Ian 
Published: March 2020

e20056 Background: This study characterizes biomarker testing over time in Non-Small Cell Lung Cancer (NSCLC) patients treated within a clinical setting. There have been tremendous advances in treatments for NSCLC that target specific biomarkers such as epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and the Programmed cell death-ligand 1 (PD-L1) pathway. As we consider using oncology EMR records for future studies, it is critical to understand the extent to which biomarker testing is conducted in routine care, the extent to which testing has increased, and the types of patients for which it is done. Methods: This is a retrospective observational analysis derived from the COTA Oncology EHR database from January 1, 2015 through December 31, 2017. The data sets generated for the study included all relevant, retrospective patient-level, de-identified data available for patients with lung cancer, including EGFR, ALK, and PD-L1 testing regardless of age, gender, and stage at diagnosis. We examined characteristics associated with each type of test received as well as by those who had received all 3 biomarker tests, 1-2 of the tests, or no biomarker testing. Analyses were conducted using SAS V. 9.1 and stratified by data source. Results: There were 1,891 patients in the COTA database. Among newly diagnosed NSCLC patients, EGFR testing has been consistently conducted in patients during the study period (76 – 86%), while ALK testing [44% in 2015Q1 to 74% in 2017Q4] and PD-L1 testing [12% in 2015Q1 to 77% in 2017Q4] have steadily increased each quarter. Overall, testing was more likely to be conducted in non-squamous cell lung cancer patients, Stage IV lung cancer, and those without a history of smoking. For EGFR, testing was more prevalent among women and young age groups ( < 64 years vs. 65 and older). Conclusions: Biomarker testing has rapidly increased for ALK and PD-L1, which correlates with the uptake of new targeted therapies. Further research could be conducted to understand clinical outcomes associated with this increase in testing as well as the impact on healthcare resource utilization.
Contemporary patterns of racial/ethnic disparities in surgical treatment and overall survival for localized resectable non-small cell lung cancer in the United States.
Authors: Akinboro Oladimeji , Nwabudike Stanley Madu , Voisine Michael , Hartshorn Kevan L. , Charlot Marjory 
Published: March 2020

e20057 Background: Racial disparities in the surgical treatment of early stage lung cancers are well documented for African-Americans relative to Whites. However, there is a paucity of contemporary data regarding lung cancer treatment disparities for other minority racial/ethnic groups. We sought to compare: i) contemporary rates of surgery, ii) and overall survival (OS) for resectable non-small cell lung cancer (NSCLC), across several minority populations in the United States (US). Methods: We identified new diagnoses of stages IA-IIIA NSCLC (AJCC7) from 2010-2015 among adults (20 years+) in the Surveillance, Epidemiology, and End Results (SEER) 18 registry. We compared rates of surgery +/- radiotherapy (RT) for stage IA NSCLC, and surgery +/- RT +/- chemotherapy for stages IB–IIIA NSCLC, among the following racial/ethnic groups: Non-Hispanic Whites (whites), Non-Hispanic Blacks (blacks), Hispanics, Asians or Pacific Islanders, and American Indians/Alaska Natives (native Americans). We also calculated and compared 5-year OS rates across these groups. Results: There were 339,912 cases of newly-diagnosed stages IA, IB, IIA, IIB, and IIIA NSCLC identified for analysis. Receipt of surgical treatment +/- RT for stage IA NSCLC was lower in blacks (63.5%), and native Americans (64.2%) than whites (69.4%), as well as for stage IIB NSCLC (whites 66.7%; blacks 56.7%; native Americans 55.6%). Blacks had lower rates of surgery relative to whites across the other NSCLC stages studied but no disparities were noted for Hispanics and Asians/Pacific Islanders. 5-year age-adjusted OS for stage IA-IIIA NSCLC were significantly lower for native Americans (62.3%, 95% CI 58.1%, 66.3%) and blacks (68.1%; 95% CI 67.4, 68.9%) relative to whites (69.2%; 95% CI 69.0%, 69.5%) with relative risks of 1.11 (95% CI 1.04, 1.19) and 1.02 (95% CI 1.01, 1.03), respectively. This inferior OS persisted for blacks even among those treated with cancer-directed surgery. Conclusions: Disparities in rates of surgical treatment and OS for resectable NSCLC persist for blacks and native Americans. Although it is unclear if inferior OS outcomes for blacks are solely attributable to lower rates of surgery, systems-based interventions are needed to help ensure equal and optimal receipt of surgery for resectable NSCLC across all racial/ethnic groups in the US.
When is a patient high risk for resection? A changing paradigm with minimally invasive lung surgery.
Authors: Nakahama Hiroko , Poulikidis Kostantinos , Lubawski James , Vigneswaran Wickii T. 
Published: March 2020

e20059 Background: The predicted post-operative forced expiratory volume after 1 second (FEV1) and the diffusing capacity of the lung for carbon monoxide (DLCO) are predictors of postoperative complications and survival. Despite the benefits of minimally invasive surgery in patients with marginal lung function current practice guidelines advocates non-surgical approach for treatment from evidence derived from patients undergoing thoracotomy. It is necessary to define what should be minimum acceptable lung function for resection in the era of minimally invasive surgery. Methods: Single institution retrospective study of 61 patients with pre-operative predicted FEV1 and DLCO < 60% that underwent lung resection for pulmonary lung nodules suspected to be malignant between January 2017 to June 2018. Patient demographic and clinical data were collected and the 30-day or in-hospital morbidity and mortality were assessed. Results: 28 (46%) patients with pre-operative predicted FEV1 < 60% and 33 (54%) with DLCO < 60% were reviewed. 10 patients had both FEV1 and DLCO < 60%. There were 12 patients (28% in FEV1, 12% in DLCO group) who had < 40% of pre-operative predicted values. 15 (65%) of FEV1 group and 15 (45%) of DLCO group had anatomic lung resections with either a lobectomy or a segmentectomy. 24 (39%) of cases were done robotically and the remaining with VATS. 80% of patients had cancer in their final pathology. Patients were 68± 7 years old, 34 (56%) were male. Significant baseline clinical findings include high incidence of smoking (82% in FEV1, 97% in DLCO group), HTN (71% in FEV1, 81% in DLCO group), COPD (61% in FEV1, 48% in DLCO group), CAD (25% in FEV1, 30% in DLCO group), and a total of 2 patients suffered previous CVD. Most common complications included persistent air leak > 5 days (21% in FEV1 and DLCO group) and arrhythmia (14% in FEV1, 15% in DLCO group). Of those with an air leak, 50% in the FEV1 group and 29% in the DLCO group had predicted values < 40%. Three patients developed pneumothorax post chest tube removal necessitating chest tube replacement, all of whom had predicted values < 40%. One patient developed acute DVT and PE and another patient required mechanical ventilation for > 48 hours. There were no 30-day mortalities. Conclusions: Lung resection using minimally invasive technique had low rates of 30-day morbidity in patients with reduced pulmonary function. Majority of complications observed were minor. Minimally invasive lung resection is possible and may be extended to selected patients with pre-operative predicted DLCO or FEV1 < 40% suspected of malignancy.