bluuebunny/crossref_metadata_2025 huggingface dataset:
Ability of routine blood tests (RBTs) in asymptomatic patients (pts) with indolent non-Hodgkin lymphoma (iNHL) to detect relapse or clinically significant disease progression.
Authors: Piercey Oliver , Loh Zoe , Chan Joanna , Chong Geoffrey , Grigg Andrew , Cheema Steven , Cushion Tania , Gill Gurjot , Whybird Matthew , Hawkes Eliza Anne
Published: March 2020

e19027

Background: Pts with iNHL undergo active surveillance to detect disease relapse or progression. International guidelines recommend regular RBTs for surveillance but evidence for this practice is lacking. Methods: We conducted a retrospective analysis of pts aged ≥16 yrs from 2008-17 undergoing routine surveillance at 2 Australian centres for grade 1-3a follicular lymphoma (FL) or marginal zone lymphoma (MZL), to assess the utility of full blood count, lactate dehydrogenase & beta-2-microglobulin to detect progression events; (i.e relapse or progression) or to change management. Abnormal results were defined as acute deviations from local laboratory normal ranges not explained by a concurrent medical condition. Eligible pts were either treatment-naive or had achieved a response to lymphoma-directed therapy, had ≥6 mths follow up and an absence of progression events within 3 mths of prior therapy. Demographic data were collected as well as treatment, follow up appointment (appt) details including presence of signs/symptoms, RBT results, survival status & further therapy. The study was ethically approved. Results: 180 eligible pts (FL:142, MZL:38) underwent 1757 follow up appts (median follow up 38 months). RBTs were done at 83% of appts. 74 progression events occurred in a total of 62 pts; 48/74 (65%) had immediate therapy. 2/74 (3%) were detected by RBTs alone, (both treatment naïve pts); 88% by signs/symptoms & 9% by routine imaging. 20/243 (8%) of abnormal RBTs in asymptomatic pts led to a change in subsequent management (10 had imaging; 8 earlier appts; 2 repeat RBTs alone). The sensitivity & positive predictive value of abnormal RBTs to detect progression events were 39% & 9% respectively. In asymptomatic patients, the number of RBTs required to change management and to detect a progression event were 64 and 644 respectively. Conclusions: RBTs rarely detect clinically significant disease progression or relapse and seldom solely lead to a change in management in asymptomatic pts with iNHL. Clinical signs/symptoms are far more likely to detect progression or relapse. Guidelines should reflect the benefit & risk of RBTs in the clinical setting.
Dominant-negative PD1-armored CART cells induce remission in refractory diffuse large B-cell lymphoma (DLBCL) patients.
Authors: Chen Tong , Yuan Yan , Huang Liansheng , Pu Chengfei , Ding Tianling , Xiao Xibin , Cao Zhiyuan , Wu Ting , Ding Luying , Sun He , Wu Zhao , Xiao Lei , Zhang Xiaohong
Published: March 2020

e19028

Background: The chimeric antigen receptor (CAR) T cell treatment has been demonstrated as an effective therapy to relapse/refractory B cell malignancy. However, tumor microenvironment influences and affects CAR T treatment. For example, programmed death ligand 1/2 (PDL1/2) may inhibit the CAR T cells via interaction with up-regulated Programmed cell death protein 1 (PD1) during T cells activation, suppressing the tumor-killing capability of the CAR T cells. Thus, blockade of the PD1-PDL1/2 interaction may enhance the anti-tumor efficacy of CAR T therapy. Methods: We generated CAR T cells including an anti-CD19 second generation (2G) CAR molecule and a dominant negative PD1 molecule (Figure A). Compared with conventional CART cells, these “armored” CART cells show the enhanced capability of tumor killing after multiple-round tumor challenging and more “memory-like” phenotypes (Figure B). These results suggest dominant negative PD1 molecules may protect CART cells from exhaustion in the tumor microenvironment. Results: We report clinical trials of three refractory diffuse large B cell lymphomas (DLBCLs) patients that were successfully treated using the armored CAR T cells described above. All of these three patients failed to achieve response after multiple rounds of chemotherapy and radiotherapy. However, after infused with autologous CART cells at 5.23×10^6/kg and 1.97×10^6/kg, respectively, they showed significant tumor mass decrease and SUV max declines in PET/CT results and ongoing responses (e.g., from 34.48 to 3.89 at day 27, from 25.02 to 2.38 at day 31, respectively, see Figure C). Conclusions: These three clinical trials revealed the significant anti-bulky lymphoma response with respect to these armored CAR T cells and limited and tolerated cytokine release syndrome and central nervous system toxicity. Also, dominant negative PD1 molecules may augment CAR T cells persistence in patients after activation by lymphoma cells, thus enhancing the efficacy of CAR T cells in the treatment of hematomas. Finally, the techniques described herein are a platform technology and may be applied to other adoptive cellular immunotherapies such as TCR-T or TIL in the treatment of solid tumors. We are continuing to recruit more patients for the clinical trials. Clinical trial information: ChiCTR1900021295.
Time to first treatment is an independent prognostic factor for multiple myeloma (MM).
Authors: Goyal Gaurav , Tella Sri Harsha , Kommalapati Anuhya , Durani Urshila , Paludo Jonas , Go Ronald S.
Published: March 2020

e19523

Background: Previous studies have shown a disparity in outcomes of MM between clinical trials and real-world practice. This could be partly due to clinical trial exclusion of patients who need urgent treatment due to high burden of disease or significant illness. In this study, we aim to analyze the impact of time to initiation of systemic therapy for MM on overall survival (OS). Methods: We included MM patients reported to National Cancer Data Base (2004-2014). We excluded 2,860 patients with suspected smoldering MM due to initial treatment beyond 120 days. Relative risk of delayed time to systemic therapy was assessed by logistic regression model. Kaplan-Meier method and Cox multivariate analysis were used to evaluate the association between time to therapy and OS. Results: A total of 53, 519 MM patients were included. Median time to systemic therapy in our cohort was 18 days (range 0-120). Of the entire cohort, 24% patients received systemic therapy for MM < 7 days from diagnosis, and 32% received it after 30 days. Factors associated with time to systemic therapy > 30 days were Black race (OR 1.12, CI 1.07-1.16), female sex (OR 1.10, CI 1.06-1.14), lower Charlson comorbidity score (OR 1.36, CI 1.28-1.45), and academic facility (OR 1.18, CI 1.13-1.24). The median OS for patients who initiated therapy > 30 days after diagnosis was longer than those who received it within 7 days (37 vs. 29 month, p < 0.001). Similarly, on multivariate analysis, patients who received treatment > 30 days after diagnosis were found to have a lower mortality as compared to those who initiated treatment < 7 days (HR 0.81, CI 0.79-0.83; Table). Conclusions: In our study, time to initiation of systemic therapy was an independent prognostic factor in MM. This could be related to the high-risk nature of disease of patients treated within a short duration of diagnosis. These findings have implications for future clinical trial design, which should allow for a pragmatic approach toward enrollment of these high-risk patients to improve external validity. [Table: see text]
Appendicular skeleton MRI in multiple myeloma: Utility and clinical implications.
Authors: Faraji Navid , Smith Daniel Arnold , Laukamp Kai , Parikh Keval , Kosmas Christos , Ramaiya Nikhil H.
Published: March 2020

e19527

Background: Skeletal MRI plays an integral role in diagnosing Multiple Myeloma and, in many cases, dictates need for treatment. While axial skeleton MRI is performed with established clinical utility, appendicular MRI is performed sparingly with utility not fully ascertained. We aim to assess the utility of appendicular MRI while establishing clinical factors which may predict outcomes. Methods: 107 appendicular skeleton MRIs were included for retrospective analysis over 15 years. No statistically significant age or gender related variability was noted. Variables including patient age, diagnosis, disease stage/activity, indication, transplant status, MRI result, treatment course, and survival were analyzed via Likelihood Ratio Chi-Square test or logistic regression. Results: Patient age, disease stage, presence of active marrow disease, history of relapse, and presence of axial or appendicular osseous disease were found to have a statistically significant correlation with MRI result. Disease stage and presence of active hematologic disease correlated with post MRI management alterations. Additionally, presence of active hematologic disease at time of MRI demonstrated a correlation with post MRI management strategy. Furthermore, MRI result was a predictor of downstream development of additional skeletal lesions. Interestingly, MRI result was not a predictor of survival. Conclusions: Several parameters may be used to determine a clinical pre-test probability of appendicular disease at the time of MRI. In addition, these clinical parameters and MRI results correlate with trends in subsequent patient treatment strategies. [Table: see text]
Role of extra corporeal methods for light chain removal on renal recovery in multiple myeloma: A systematic review.
Authors: Hassan Hamza , Rafae Abdul , Iftikhar Nimra , furqan fateeha , Iftikhar Ahmad , Mushtaq Adeela , Ashraf Afia , Majeed Ammara , Kashinath Sanjana , Razzaq Faryal , Anwer Faiz
Published: March 2020

e19530

Background: Renal impairment (RI) in Multiple Myeloma (MM) adversely affects the prognosis. Removing circulating free light chains via hemodialysis (HD) or plasma exchange (PLEX) along with chemotherapy can improve renal outcomes in MM. Methods: Per PRISMA guidelines a systematic search yielded 7311 articles since 2009 on 4 databases. After screening, 16 studies were included. Results: Main modalities were high cut off (HCO) HD, high flux (HF) HD, conventional HD and PLEX. N = 541 patients underwent HD/PLEX. 375/541 (69.3%) patients received HCO HD. In 2 RCTs, there was no significant difference in renal recovery (55.8% vs 51.6%; 41% vs 33%). The overall survival (OS) between the 2 groups was lower in the HCO group vs conventional HD (55.8% vs 76.6%) at 2 years while there was no significant difference in second study. Conclusions: HCO has failed to show promising efficacy with 2 RCTs failing to show statistical OS difference. There is paucity of data and further trials are needed. [Table: see text]
Impact of autologous stem cell transplant in myeloma patients on renal function and overall survival.
Authors: Abudayyeh Ala , Abdelrahim Maen , Lin Heather Y. , Saliba Rima , Martinez Charles , Delgado Ruby , Page Valda D , Sanders Paul W , Qazilbash Muzaffar H.
Published: March 2020

e19535

Background: Renal impairment has been negatively associated with progression free survival and overall survival in patients diagnosed with multiple myeloma (MM). Autologous stem cell transplant (ASCT) has become a standard of care for treatment in MM. Most previous studies have assessed the safety of ASCT and the improvement in renal function in patients with MM. However, a critical question about renal function over time, and its impact on survival after ASCT has rarely been addressed. In our study we sought to understand how renal function was impacted over time, the predictors of renal function, and overall survival after ASCT. Methods: We performed a retrospective review of all MM patients who underwent ASCT at MDACC from January1, 2008 through December 31, 2013. A total of 885 none dialysis patients who received Melphalan alone as the conditioning regimen were identified. We collected demographic information, ISS stage, and disease status at time of transplant and at last follow up. Creatinine, GFR (calculated using CKD Epi equation), calcium, and LDH were also collected at day 0, 100, 180, & 365. Given the longitudinal nature of the data, linear mixed effect models were used to study the change of GFR over time. A joint model approach for longitudinal and survival data was used to assess association between overall survival and GFR with patient’s age at transplant, ISS, disease status, disease risk category and response to treatment prior to transplant included in the linear mixed effect models and hazard models. As sensitivity analyses, landmark analyses were conducted with day 0, 100, 180, and 365 days post-transplant as landmark time points. Results: Patients’ GFR at post-transplant time points were significantly higher (p ≤ 0.025) compared to the day of ASCT. A higher ISS stage at diagnosis was significantly associated with a lower GFR (p < .0001) at all stages of chronic kidney disease. Specifically, compared to the patients with ISS stage I, those with ISS stage II or higher had lower GFR across all time points (p ≤ .0003). GFR value was not significantly associated with OS in any of the analyses described above. In contrast, disease status, ISS stage, response to induction prior to SCT were all associated with shorter OS. Conclusions: The study demonstrates in a large cohort and in a longitudinal manner that MM patients who underwent ASCT did not have further decline in GFR over time. In addition, GFR was strongly associated with ISS stage. As far as OS, MM-related factors significantly impacted the survival while GFR did not.
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.
Exploring sex differences in small cell lung cancer: Is this a hormonal issue?
Authors: Duma Narjust , Ho Thanh P. , Durani Urshila , Funni Shealeigh , Inselman Jonathan , Paripati Harshita , Adjei Alex A. , Molina Julian R. , Mansfield Aaron Scott
Published: March 2020

e20077

Background: Small cell lung cancer (SCLC) accounts for about 10% to 15% of lung cancers among women and men. Though heavily associated with smoking, its incidence in women is rapidly increasing despite a decline in cigarette exposure. Given the changing demographics of SCLC and hormonal factors associated with other forms of lung cancer, we studied differences between sexes in SCLC. Methods: Utilizing the National Cancer Database, we identified all incident SCLC cases from 2004 to 2014. Patients were classified as limited stage (LS) or extensive stage (ES). Women were stratified by menopausal status (≥55 years = postmenopausal). Kaplan-Meier method and Cox regression were used for overall survival (OS) and multivariable analysis. Results: 161,978 patients were identified. No significant sociodemographic differences were observed between sexes. The majority of patients were non-Hispanic whites (89.1%), followed by non-Hispanic blacks (7.5%). Men were more likely to be diagnosed with ES disease than women (63% vs. 56%). Both sexes initiated treatment within a similar time frame from diagnosis (chemotherapy, median: 18 days, IQR 8-32). Women had better median OS compared to men in both LS (15.2 vs. 12.7 months, HR: 0.85, 95% CI 0.83-0.86, p < 0.0001) and ES (6.4 vs. 5.7 months, HR: 0.88, 95% CI 0.87-0.90, p < 0.0001). No racial or ethnic disparities in OS were observed, overall and when examined within sex and disease stage groups. Differences between sexes in OS were also observed when comparing patients within the same racial/ethnic group (women having better OS). When divided by menopausal status, postmenopausal women with LS and ES had worse OS than premenopausal women (14.7 vs. 22 months, HR: 1.50, 95% CI 1.44-1.56; 6.1 vs. 9.8 months, HR: 1.41, 95% CI: 1.37-1.46, respectively). We also observed worse OS in older men when divided by age ( < 55 years and ≥55 years). In multivariable analysis, older age, postmenopausal status, and Medicaid as primary insurance were associated with worse OS for both LS and ES. Conclusions: In this large cohort, women with SCLC had better OS compared to men. Post-menopausal women had worse OS compared to pre-menopausal women. Since older men had a similar trend of worse survival compared to younger men, age might exert a more significant influence on survival than hormonal status in SCLC. Further studies with data on sexual hormone levels are necessary to better understand their role in women with SCLC.
Radiologic imaging utilization of small cell lung cancer staging and treatment.
Authors: Kikano Elias , Bomberger Thomas , Shinagare Atul B. , Laukamp Kai , Dowlati Afshin , Ramaiya Nikhil H.
Published: March 2020

e20079

Background: Over the past several decades, first line therapy recommendations for small cell lung cancer (SCLC) have remained relatively unchanged. Additionally, the National Comprehensive Cancer Network (NCCN) guidelines regarding initial evaluation, staging, response assessment, and surveillance of SCLC have also remained relatively static. To evaluate radiologic imaging utilization for SCLC, we reviewed patients imaging data and assessed their association with staging, metastatic sites at presentation, overall survival, and other clinical factors. Methods: Retrospective analysis of patients with a diagnosis of SCLC that received treatment and follow up from 2003 through 2018 was completed. Cross-sectional radiology imaging data including computed tomography of the chest abdomen and pelvis (CT CAP), magnetic resonance imaging (MRI), and positron-emission tomography (PET) was obtained from the picture archiving and communication system (PACS) and clinical data including age, sex, race, smoking history, extensive/limited stage, and metastatic sites at presentation was obtained from the electronic medical record. Results: The average age at diagnosis for all SCLC patients (n = 518) from 2003 to 2018 was 66 with a male to female ratio of 0.89. The mean overall survival of all SCLC patients was 410.2 days with extensive (n = 371) stage = 312.5 days and limited (n = 147) stage = 718.8 days. We found a significantly increased number of patients less than age 66 presented with brain metastasis compared to those greater than age 66 ( P< 0.01). The absolute total number of CT CAP and PET studies was significantly increased in limited stage patients compared to extensive stage ( P< 0.001). However, when accounting for mean overall survival, extensive stage patients received a significantly increased number of CT Brain ( P< 0.05), PET ( P< 0.01), CT CAP, and MRI Brain ( P< 0.001) studies compared to limited stage per year. Conclusions: Overall radiology imaging utilization is significantly different between limited and extensive stage SCLC patients over the past 15 years.
Prognostic impact of paraneoplastic syndromes in patients with small cell lung cancer, real-world data.
Authors: Picard Leblanc Gabrielle , Blais Normand , Tehfe Mustapha , Routy Bertrand , Florescu Marie
Published: March 2020

e20082

Background: Small cell lung cancer (SCLC) remains an aggressive cancer, with a reported mOS of 15-20 mo when localized (L-SCLC) and 9-11 mo when extensive (E-SCLC). Paraneoplastic syndromes (PNS) are a debilitating condition either related to the embryogenic stem cell origin or to auto-immune antibodies produced against the tumor. These mechanisms may be even more relevant with the use of immunotherapy for first-line treatment of E-SCLC. Methods: We retrospectively reviewed our clinical database of patients diagnosed with SCLC between 2006 and 2017 at CHUM University Center. The primary outcome was to compare OS of patients with and without PNS in L-SCLC and E-SCLC. No patients received immunotherapy. Results: We identified 426 unselected SCLC patients, 39% L-SCLC and 61% E-SCLC. 84 patients (20%) were diagnosed with a PNS: 66 (15%) SIADH, 8 (2%) paraneoplastic Cushing syndromes, 2 (1%) humoral hypercalcemia and 8 (2%) paraneoplastic neurologic syndromes. 25% of patients with PNS vs 14% without PNS had a PS 3-4 and would not have been eligible to a clinical trial. 65% of patients with PNS received chemotherapy vs 63% without PNS. Neurologic PNS were all diagnosed in patients with L-SCLC. PNS affecting the central nervous system (4 limbic encephalitis and 1 cerebellar degeneration) were associated with a poorer prognosis than L-SCLC without PNS (mOS 3,5 mo vs 16,7 mo (p = 0,003)). The 2 patients with Lambert-Eaton myasthenic syndrome had a long survival (29 and 82 mo), but persistence of the neurologic symptoms. 86% of patients with paraneoplastic Cushing syndrome were diagnosed with an E-SCLC and had a worse prognosis than E-SCLC without PNS (mOS 1,1 mo vs 4,63 mo (p = 0,022)). SIADH had a significative poor impact on OS in patients with L-SCLC (mOS 10,1 mo vs 16,7 mo (p = 0,016)), but no impact in survival for patients with E-SCLC (mOS 3,63 mo vs 4,63 mo (p = 0,735)). Conclusions: PNS either in patients with L-SCLC or E-SCLC worsen the overall prognosis, except for Lambert-Eaton myasthenic syndrome. A more systematic detection of these syndromes is suggested before starting immunotherapy as first-line standard treatment for E-SCLC. Furthermore, this real-world unselected clinical cohort shows our E-SCLC patients have a worse prognosis than the clinical trial experience.
Cost-effectiveness analysis of atezolizumab plus chemotherapy in the first-line treatment of extensive small cell lung cancer in China.
Authors: Li Lingyu , Wang Hong , Li Wenqian , Cui Jiuwei
Published: March 2020

e20083

Background: Atezolizumab plus chemotherapy as a first-line therapy has shown significant survival benefits in patients with extensive small-cell lung cancer (SCLC). While, overprice limited its broad use in clinical. Here, the aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China. Methods: A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients. Utility values were obtained from published studies, and the costs were acquired from real world and literature. Additionally, sensitivity analyses based on a willingness-to-pay threshold (WTP) were performed to identify the uncertain parameters of Markov model. Results: Total costs of atezolizumab group was $183801, while cost of chemotherapy alone group was just $12920 in placebo group. The QLAYs in atezolizumab group was just 1.15 higher than that in placebo group (13.73 QALYs vs. 12.58 QALYs). The ICER between atezolizumab combination with chemotherapy and chemotherapy alone was $148592/QALY in China. The net benefit of placebo group was significantly higher than atezolizumab group. One-way sensitivity analyses highlighted that utilities of the PFS and PD state in placebo group were the most influential parameter. Conclusions: Atezolizumab combination therapy was not more cost-effective than chemotherapy alone therapy at a WTP threshold of $25929/QALYs in China.
The concomitant EGFR T790M/C797S in trans and cis in three osimertinib-resistant lung adenocarcinoma patients.
Authors: Liu Chunling , Li Jidong , Liu Hailong , Du Rong , Fang Nan , Zhang Jingbo , Tang Yu , Wang Jianwei , Wu Qixi
Published: March 2020

e20105

Background: EGFR C797S mutation is an important cause of Osimertinib resistance. Previous studies showed that patients harboring EGFR C797S in trans with T790M are sensitive to a combination of first- and third-generation EGFR tyrosine kinase inhibitors (TKI). However, patients harboring EGFR C797S in cis with T790M are resistant to combination therapy or each single reagent. Methods: We performed next-generation sequencing on peripheral blood samples from patients with advanced lung adenocarcinoma who had been undergoing targeted therapy. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 14 lung cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina MiSeq 500 platform. Results: Among 6489 Lung adenocarcinoma patients sample, we identified concomitant trans and cis EGFR T790M/C797S in three patients with very poor prognosis. All three patients were sensitive to the first-generation EGFR TKI, and took Osimertinib when disease progressed. When resistant to Osimertinib, the patients went to genetic testing to find new target therapy. Patient No. 1 was a 66-year-old man with mutations of EGFR exon 19del (25.08%), EGFR T790M (10.08%) / C797S (5.37%) in trans and in cis, TP53 exon8 mutation (12.35%). This patient died 20 days after the genetic testing without any further treatment. Patient No. 2 was a 53-year-old woman who carried gene mutations including EGFR exon 19del (0.51%), EGFR T790M (0.57%) and C797S (0.47%) in trans and in cis. She was treated with the combination of first- and third-generation EGFR TKI, and disease progressed after 50 days. She died half months after the gene test. Patient No. 3 was a 63-year-old woman whose gene mutation included EGFR L858R (77.49%), EGFR T790M (40.94%) and EGFR C797S (5.46%) in trans and in cis, also combined with EGFR amplification. Treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor Anlotinib was attempted, but the patient died within one month after the gene test. Conclusions: We firstly reported three cases with concomitant EGFR T790M/C797S in trans and EGFR T790M/C797S in cis mutation in the word. Physicians tried either the EGFR TKI inhibitor combination therapy or VEGFR inhibitor, but neither of them had an effect on these patients. All three patients had very poor prognosis and died within two months of the gene test, indicating that the concomitant of the cis and trans mutation could be a very important prognostic prediction factor.