tbuckley/cabot-search huggingface dataset:
Neoadjuvant treatment of adenocarcinoma of the rectum: Historical analysis and correlation between pathological regression rate and the outcomes.
Authors: Jeziel Basso, Sergio Jobim Azevedo, Marta Nassif Pereira Lima, Daniel C. Damin, Pedro Emanuel Rubini Liedke, Luis Fernando Moreira, Fernando de Souza Pereira, Rodrigo Perez Pereira
Journal: Journal of Clinical Oncology (2019)

e15177 Background: Treatment of locally advanced rectal cancer is based on chemoradiation associated with surgery. This treatment has high potential for curability. Tumor regression grade appears to be a prognostic factor and be influenced by the timing of surgery. Methods: A retrospective database was formed. We included patients submitted to neoadjuvant chemoradiotherapy and rectal surgery, treated at the Hospital de Clínicas, Porto Alegre. We analyzed outcomes, pathologic and treatment toxicity data. TRG was mensurated by the modified Ryan method, as the AJCC. We sought to analyze the better timing for surgery after chemotherapy, comparing the weeks after surgery with the rate of pCR. Statistical analysis was done with Kaplan Meier, Pearson's Chi-square and the Cox regression method. Results: We accrued 156 patients between 2006 and 2018. The rate of PFS at 3 and 5 years were 75% and 70%, respectively. The 5-year overall survival was 91%. The rate of pCR was 12.8%. TRG was an important prognostic factor. The absence of a pathological response (TRG 3) was associated with an increase in mortality, HR 3,148 (95% CI 1.6-12.2 P 0.003) and a decrease in PFS, HR 3,148 (95% CI 1, 7-5.8 P 0.0001). The 5-years PFS with TRG 0,1, 2 and 3 were 95%, 87%, 73.3% and 48%, respectively. Comparing the time between neoadjuvant treatment and surgery of less than 8 weeks versus 8 and 12 weeks versus above 12 weeks, the rates of pCR were 4.3%, 18.6% and 7.1% and the rates of TRG 3 were 32,6%, 18,6% and 57,1% (P 0.016). The chemotherapy regimens included 5FU bolus (75.1%) and capecitabine (19.1%). Doses of radiotherapy above 45 Gy were received by 80.5% of patients. Adjuvant treatment was not performed in 30.6% and 16.6% of these cases had positive pathological lymph nodes. The grade 3/4 adverse event rate was 21.6%. Conclusions: The outcomes found are favorable. The pathological tumor regression grade is an important prognostic factor. New strategies such as total neoadjuvant may play a role considering the rate of patients who cannot perform adjuvant chemotherapy. The time after neoadjuvant treatment seems to influence the tumor regression rate, especially between 8 and 12 weeks.
Generating real-world evidence: Using automated data extraction to replace manual chart review.
Authors: Jennifer H. Law, Christopher Pettengell, Lisa W Le, Steven Aviv, Patricia DeMarco, David C. Merritt, Sally CM Lau, Adrian G. Sacher, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2019)

e18096 Background: Real world evidence is a valuable resource to help guide clinical care beyond evidence generated from clinical trials, for example safety and effectiveness of novel treatments in special populations. Administrative databases often lack sufficient clinical detail to address gaps in the improvement of patient management and quality of care. Detailed clinical data collection and curation are resource intensive, limiting the ability to generate and maintain large informative cancer databases. Darwen, novel technology developed by Pentavere, enables the automation of data abstraction from unstructured hospital electronic medical records and may eliminate the need for manual chart review. Methods: Health records were identified through an institutional cancer registry from patients with stage IIIB/IV lung cancer (NSCLC or SCLC) diagnosed and treated at the Princess Margaret Cancer Centre between 01/01/2015 and 31/12/2017. Cases underwent automated data extraction including demographics, comorbidities, treatment, concurrent medications and outcomes until 30/06/2018. Agreement with data fields extracted using manual data collection in an external validation set of patients is planned. Results: Of 1210 patients identified, 538 were eligible for analysis. From automated data abstraction, 9.9% were reported to have SCLC, 67.5% adenocarcinoma, 11.2% squamous carcinoma, 28% EGFR mutations, 5.8% ALK fusions and 9.3% tumour PDL1 &gt; = 50%. Of the 304 (56.5%) that received systemic therapy, initial treatment was chemotherapy for 55.6%, targeted therapy in 34.2% and immunotherapy in 10.2%. Additional outcome data and agreement with manually curated data fields will be presented. Conclusions: Automated software to extract clinical data is a powerful new tool to generate and maintain databases that yield high quality real world clinical evidence. This is a critical next step to improve clinical decision making, inform evidence-based practice and improve quality of cancer care.
Impact of adjuvant chemotherapy and cumulative cisplatin dose in locally advanced nasopharyngeal carcinoma (LA-NPC) treated with definitive chemoradiotherapy.
Authors: Marc Oliva Bernal, Shao Hui Huang, Rachel Taylor, Jie Su, Wei Xu, Aaron Richard Hansen, Raymond Woo-Jun Jang, Andrew Bayley, Ali Hosni, Meredith Elana Giuliani, Jolie Ringash, Scott Victor Bratman, John Cho, Jonathan Crawford Irish, John Waldron, Ilan Weinreb, John Kim, Brian O'Sullivan, Lillian L. Siu, Anna Spreafico
Journal: Journal of Clinical Oncology (2019)

6046 Background: Total cumulative cisplatin dose (CDDP-D) (concurrent/induction/adjuvant) in multimodality therapy for LA-NPC has been associated with survival at centers in Asia. We evaluated the survival impact of adjuvant chemotherapy (adj chemo) and total CDDP-D in a large, single institution Canadian cohort of LA-NPC. Methods: Patients (Pts) withWHO type II and III LA-NPC treated with concurrent IMRT with high-dose CDDP and adj chemo with CDDP/Carboplatin and 5-FU (maximum total/adjuvant CDDP-D= 540/240 mg/m 2 ) between 2003-2016 were analyzed. EBER status was tested by ISH. Staging was classified by UICC/AJCC7 th edition TNM. Kaplan-Meier 5-year (5y) for overall survival (OS) and recurrence-free survival (RFS) were calculated and compared by log-rank test betweenstage, adj chemo (yes vs no) and total CDDP-D (&gt;300 vs ≤300mg/m 2 ). Multivariable analysis (MVA) identified survival predictors. Results: A total of 312 pts were evaluated: median age = 49.8 (range 17.4-75.9); EBER+/-/unknown=67%/1%/32%; stage II/III/IV=2%/51%/47%; T4=36%; N3=17%; adj chemo=83% (21% switched to carboplatin); median total/adjuvant CDDP-D=380/160 mg/m 2 ; median follow-up 7.6 years (range 0.6-14.9). 5y OS differed by stage II-III vs IV (95% vs 80%, p&lt;0.001) and total CDDP-D &gt;300 vs ≤300mg/m 2 (89% vs 83%, p=0.02). Adj chemo and total CDDP-D impacted 5y OS in stage IV (table). 5y RFS was higher in stage IV with total CDDP-D &gt;300 vs ≤300mg/m 2 (74% vs 59%, p=0.03), with a trend in locoregional control (LRC) (91% vs 80%, p=0.05) but not significant on distant control (DC) (78% vs 72%, p=0.36). Conclusions: Total CDDP-D &gt;300 mg/m 2 impacts OS in the overall cohort. The benefit of adj chemo and total CDDP-D on OS and RFS is significant in stage IV but not stage II-III LA-NPC, mainly due to higher LRC rather than DC. [Table: see text]
POLEM: Avelumab plus fluoropyrimidine-based chemotherapy as adjuvant treatment for stage III dMMR or POLE exonuclease domain mutant colon cancer—A phase III randomized study.
Authors: David Lau, David Cunningham, Angela Gillbanks, Richard Crux, Rachel Powell, Eleftheria Kalaitzaki, Nicola E. Annels, Francesco Sclafani, Marco Gerlinger, Ian Chau, Ian Tomlinson, Naureen Starling, Hardev S. Pandha, David N. Church, Tony Dhillon
Journal: Journal of Clinical Oncology (2019)

TPS3615 Background: Colon cancer with deficient mismatch repair (dMMR) and POLE mutations are characterised by a high tumor mutational burden (TMB) and an immunogenic lymphocyte infiltrate. Approximately 12% of stage III colon cancer have dMMR. POLE mutations occur in 1% of colon cancers, but is enriched in patients &lt;50 years of age. Colon cancer with high TMB have demonstrated to be sensitive to immune checkpoint inhibition in the metastatic setting. We are conducting a phase III randomised trial to determine if the addition of the anti-PD-L1 antibody, avelumab following adjuvant chemotherapy can improve disease free survival (DFS) in patients with stage III colon cancer with dMMR or POLE mutations. Methods: We are recruiting patients with curatively resected, stage III colon cancer which are dMMR or have a centrally confirmed POLE exonuclease domain mutation. Eligible patients are randomised in a 1:1 ratio to standard fluoropyrimidine-based chemotherapy (CAPOX [capecitabine, oxaliplatin] for 12 weeks or capecitabine for 24 weeks) or chemotherapy followed by avelumab (10mg/kg, 2 weekly for 24 weeks). Stratification is by chemotherapy received and MMR status. The primary endpoint is DFS. Secondary endpoints include overall survival, toxicity, quality of life, and health resource use. Exploratory objectives will investigate circulating, tumor and stool based biomarkers of avelumab benefit. The 3-year DFS rate in the control arm is expected to be ~75%. Avelumab is expected to improve the 3-year DFS rate by 12% (i.e. 87%). Target accrual is 402 patients which provides 80% power to detect a hazard ratio of 0.48 for DFS at a two–sided alpha of 0.05. This trial is a national, multi-centre phase III trial and it is anticipated that approximately 40 centres in the UK will participate. This study opened to recruitment in August 2018. Clinical trial information: NCT03827044.
Immune-checkpoints inhibitors in metastatic non small cell lung cancer with rare histology.
Authors: Diego Signorelli, Roberto Ferrara, Claudia Proto, Giuseppe Lo Russo, Martina Imbimbo, Giulia Galli, Alessandro De Toma, Filippo Pagani, Giovanni Randon, Giovanni Fucà, Benedetta Trevisan, Monica Ganzinelli, Nicoletta Zilembo, Alessandra Fabbri, Filippo G. De Braud, Marina Chiara Garassino, Arsela Prelaj
Journal: Journal of Clinical Oncology (2019)

9106 Background: Immune-checkpoints inhibitors (ICIs) have clearly improved prognosis of metastatic lung squamous carcinoma and adenocarcinoma, while their benefit remains uncertain in patients (pts) with rare NSCLC histotypes (RH). The study aim was to evaluate ICIs efficacy in RH. Methods: We retrospectively collected data from consecutive metastatic NSCLC pts treated with ICIs at our Institution from 4/2013 to 12/2018. Objective response rate (ORR) and disease control rate (DCR) were assessed. Fisher’s exact test was used to compare ORR and DCR in RH versus not-RH (NRH). Univariate and multivariate survival analyses were estimated by Kaplan-Meier and Cox progression hazard models. Results: Of 268 pts, 31 (11.6%) had RH: 16 sarcomatoid, 7 pulmonary enteric adenocarcinoma, 4 large cell neuroendocrine carcinoma and 4 adenosquamous carcinoma. In RH group, median age was 67 years old (range 41-81), most were males (71%) and smokers (90.3%); ECOG PS was: 0 (16.1%), 1 (67.8%) and 2 (16.1%). PD-L1 &lt; 1%, 1-49%, ≥50% and unknown expression were reported in 22.6%, 19.3%, 35.5% and 22.6% pts, respectively. Twelve pts received ICIs as first and 19 as second or further-line. ORR was 22.6% in RH, 20.3% in NRH (p = 0.81); DCR was 35.5% in RH, 53.1% in NRH (p = 0.08). After a median follow-up of 20 months (m) (95% CI 4.0 – 36.7 m), median progression-free survival (PFS) was 2.6 m (95% CI 1.9-3.3 m) in RH vs 2.6 m in NRH (95% CI 2.1 – 3.0 m); median overall survival (OS) was 4.6 m (95% CI 0.03-12.0 m) in RH vs 9.2 m (95% CI 7.4 – 10.9 m) in NRH. No statistically significant differences were seen between the two groups (p = 0.729 for PFS, p = 0.601 for OS). At multivariate analyses adjusted for age, sex, smoke, PS, PD-L1 status, line of therapy and histotype (RH vs NRH), only low PS and first line treatment showed better PFS and OS (p &lt; 0.001 and p = 0.003, respectively) in overall population. Conclusions: Our analysis, limited by the small and heterogeneous RH sample size, reported no significant differences between RH and NRH in terms of ORR, DCR and survival. However, looking at OS and DCR data, RH seem to have worse outcome. Correlation between histotype and pts characteristics and survival analyses in a larger cohort of ICIs treated NSCLC pts is ongoing. Specific prospective trials are needed to evaluate ICIs role in RH.
Autoantibodies indicating diagnostic or prognostic value in NSCLC patients were identified by protein microarrays.
Authors: Rongrong Luo, Caixia Liang, Jiarui Yao, Di Wu, Zhishang Zhang, Yuankai Shi, Xiaohong Han
Journal: Journal of Clinical Oncology (2019)

e20638 Background: Autoantibodies(AAbs) have been recently recognized as auxiliary diagnostic biomarkers in lung cancer. Applying high-throughput protein microarrays to address AAbs profile of non-small cell lung cancer(NSCLC) is rarely studied. Herein, we aimed to discover AAbs possessing diagnostic or prognostic value in NSCLC patients. Methods: We collected pretreatment plasma samples and survival data of 258 NSCLC patients and 343 controls. The advanced NSCLC patients were divided into subgroups according to different epidermal growth factor receptor(EGFR) gene status, therapies and therapeutic response. We utilized human proteomic(HuprotTM) microarrays to screen differential AAbs and customized microarrays to validate. Statistical methods were Chi-square test and ROC analysis. Results: We found 8 AAbs(p &lt; 0.05 or AUC &gt; 0.6) with underlying diagnostic or prognostic value of NSCLC patients after screening and validation. The positive rate of 4 AAbs including anti-TP53, XAGE1A1,2 and KCNAB1 in NSCLC group were higher than that in controls. Among them, anti-KCNAB1 increased in early-stage group compared with controls, indicating early diagnostic value. The other three AAbs level raised as disease progressed to advanced-stage. For advanced NSCLC patients, the differential AAbs of EGFR+ patients receiving either first generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy or chemotherapy were identified with higher positive rate in poor response subgroups compared with good response subgroups(Table1). However, for EGFR- patients with chemotherapy, the differential AAbs in different response subgroups were not found. Conclusions: We found AAbs with underlying diagnostic or prognostic value for advanced NSCLC patients receiving EGFR-TKI or chemotherapy, which should be further investigated to confirm their clinical value. [Table: see text]
Comparison of outcomes in a population-based cohort of women with metastatic breast cancer receiving anti-HER2 therapy with clinical trial outcomes.
Authors: Inna Y. Gong, Andrew T Yan, Maureen E. Trudeau, Andrea Eisen, Craig Earle, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2019)

1037 Background: Little data exist for comparing cardiac safety and survival outcomes of anti-HER2 therapy with concurrent trastuzumab (T) and pertuzumab (P) or ado-T emtansine (TDM1) in metastatic breast cancer (MBC) patients enrolled in randomized clinical trial (RCT) vs those in the real world. Furthermore, whether older patients have worse outcomes is unknown. Methods: This was a retrospective population-based cohort of all women with MBC treated with concurrent T with P or TDM1 in Ontario (between 2012 and 2017), identified from New Drug Funding Program and linked to Ontario Cancer Registry and other administrative datasets. Outcomes were incident heart failure (HF, defined as hospitalization or emergency room visit for HF) and overall survival (OS). RCT data were obtained from digitizing survival curves as per established methods and compared with cohort OS data using log-rank test. Age based comparison of outcomes was conducted for women ≥ 65 years old vs younger. Results: Our cohort composed of 833 (28% &gt; 64 years old), and 397 (28% &gt; 64 years old) women treated with P and TDM1, respectively, of which 46 and 30 had baseline HF, respectively. 49% and 99.5% of women received T prior to P and TDM1, respectively. Incident HF following P or TDM1 initiation was low (P 26 women, TDM1 8 women; Table). HF events was not more in women ≥ 65 years old compared to women &lt; 65 treated with P (16 vs. 10, p = 0.23). Unadjusted OS was significantly worse than RCT OS (Table; P HR 1.67, 95% CI 1.37-2.03, p &lt; 0.0001; TDM1 HR 2.80, 95% CI 2.27-3.44, p &lt; 0.0001). Older women had worse OS than younger women for P (HR 1.54, 95% CI 1.22-1.96, p = 0.0003), but not for TDM1 (HR 1.08, 95% CI 0.81-1.43, p = 0.62). Conclusions: HF incidence during P or TDM1 therapy in this real world cohort was relatively low. Survival in this cohort was significantly worse compared to RCT, particularly for older women, suggesting importance of evaluating effectiveness in an unselected patient population to facilitate informed decision-making based on real-world risks and survival outcomes.[Table: see text]
Time-to-treatment discontinuation (TTD) and real-world progression-free survival (rwPFS) as endpoints for comparative efficacy analysis between entrectinib trial and crizotinib real-world <i>ROS1</i> fusion-positive (<i>ROS1</i>+) NSCLC patients.
Authors: Robert Charles Doebele, Laura Perez, Huong Trinh, Michael Martinec, Reynaldo Martina, Todd Riehl, Matthew Krebs, Neal J. Meropol, William Bruce Wong, Gracy Crane
Journal: Journal of Clinical Oncology (2019)

9070 Background: Entrectinib is an oral tyrosine kinase inhibitor for ROS1+ NSCLC. Three phase 1/2 single-arm studies showed entrectinib efficacy in this population (Doebele WCLC 2018). Due to the rarity of ROS1+ pts generating direct comparative evidence in prospective randomized trials is difficult. We identified a retrospective real-world cohort of ROS1+ NSCLC pts from electronic health records (EHR), to compare crizotinib, the current standard of care, to entrectinib as reported in clinical trials. Methods: Crizotinib-treated pts with advanced ROS1+ NSCLC diagnosed 1 Jan 2011 to 30 Jun 2018, were identified with technology-enabled abstraction in the Flatiron Health EHR-derived database ( &gt; 2.1 million cancer pts from US oncology practice). Entrectinib trial inclusion/exclusion criteria were applied to match the crizotinib cohort as closely as possible. Primary endpoint: TTD, adapted from Gong (ASCO 2018); rwPFS (physician/scan report) and OS were secondary outcomes. Time-to-event analyses used Kaplan-Meier survival curves and Cox proportional hazard models on propensity score weighted populations; age, gender, race/ethnicity, smoking status, brain metastasis and previous lines of therapy were prognostic factors. Results: We analyzed 53 entrectinib and 69 crizotinib ROS1+ NSCLC pts. Median weighted TTD: entrectinib, 14.6 mo (95% CI: 8.3–23.8); crizotinib, 8.8 mo (95% CI: 8.2–9.9). When rwPFS from crizotinib was compared to trial PFS, entrectinib had longer PFS vs crizotinib (weighted HR: 0.44; 95% CI: 0.27–0.74). Median OS with entrectinib was not reached (median follow-up: 15.5 mo); weighted median OS with crizotinib was 18.5 mo (95% CI: 15.1–19.9). Findings were consistent across multiple sensitivity analyses. Conclusions: Entrectinib was associated with longer TTD and PFS in ROS1+ NSCLC pts vs a matched real-world crizotinib population. Control populations derived from real-world cohorts can supplement evidence from clinical trials in settings where new standards of care are needed, but where only limited data are available and randomization is not feasible.
Neutrophil-to-lymphocyte ratio and subsequent recurrence of non-small cell lung cancer patients in remission.
Authors: Abigail Sy Chan, Søren Bentzen, Michael L Adashek, Joseph Friedberg, Melissa Culligan, Tamara Khashab, Kenneth David Miller
Journal: Journal of Clinical Oncology (2019)

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&lt;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]