tbuckley/cabot-search huggingface dataset:
Evaluation of treatment strategies in stage II and III rectal cancer: An NCDB Analysis.
Authors: Shreya Sinha, Nibal Saad, Wajihuddin Syed, Lauren Panebianco, Adham Adel Jurdi
Journal: Journal of Clinical Oncology (2018)

e15677 Background: Patients with T3, N0 or any T with N1-2, or T4 rectal cancer should proceed with either concurrent chemo-radiation (CRT), radiation therapy (RT) alone or chemotherapy (CT) followed by CRT in the neoadjuvant (NA) setting. In the latter, the benefit of adjuvant CT is not well defined. Using the National Cancer Data Base (NCDB), we report the impact of different treatments in stage II and III rectal cancer on overall survival (OS). Methods: Patients with stage II and III rectal cancer were identified in the NCDB from 2004-2015 of age > 18. Three different patient cohorts were identified: group 1 received NA CRT then underwent surgery; group 2 received NA CRT, surgery and then adjuvant chemotherapy; and lastly, group 3 did not receive NA treatment, underwent surgery and received adjuvant chemotherapy. Kaplan Meier curve were constructed for calculation of OS with hazard ratio (HR) estimated from cox model. Log rank test was used for comparison between groups. Groups were compared for OS benefit at 1 year, 5 year, and 10 years from diagnosis. Results: A total of 65,836 patients meeting the criteria were included in the analysis. Of these patients, 44,883 (68.17%) received NA CRT followed by surgery with no adjuvant treatment. 19,100 (29.01%) received NA CRT, surgery, then adjuvant chemotherapy, and only 1,853 (2.81%) received surgery and adjuvant chemotherapy. The difference in OS was significant between the three groups with p-value < 0.0001. Patients in group 2 had better OS compared to the patients that did not get adjuvant chemotherapy at 1, 5 and 10 years with HR 0.725 [CI: 0.698-0.752]. Patients who received NA CRT had better OS compared to patients who underwent surgery with no NA treatment even though both cohorts received adjuvant chemotherapy with HR 0.758. This advantage disappears when the NA CRT group did not receive adjuvant chemotherapy after surgery [HR 1.046]. Survival rates at 5 years for group 1 was 69.7%, group 2 was 76.4%, and group 3 was 71.1%. Conclusions: Although there are multiple treatment strategies for patients with stage II and III rectal cancer, we found that patients who received NA CRT followed by surgery and then adjuvant chemotherapy had best OS.
A preoperative nomogram for tumor regression grade following induction chemotherapy for esophageal squamous cell carcinoma.
Authors: Xiaozheng Kang, Liang Dai, Wanpu Yan, Yongbo Yang, Haitao Zhou, Hao Fu, Heli Yang, Mengying Fan, Yao Lin, Zhen Liang, Hongchao Xiong, Ke-Neng Chen
Journal: Journal of Clinical Oncology (2017)

e15525 Background: To (1) evaluate the continuous distribution of tumor regression grade (TRG) in resection specimens after induction chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), (2) determine the effects of TRG on survival after esophagectomy, and (3) identify preoperative predictors of TRG. Methods: From June 2001 to October 2012, 212 patients underwent induction chemotherapy followed by esophagectomy for locally advanced ESCC. TRG, assessed as the percentage of residual primary ESCC cells in resection specimens, was classified histologically by pathologists. Random Forest technology was used for data analysis. A nomogram was developed allowing prediction of TRG through use of preoperative clinical factors for patients with clinically locally advanced ESCC who are candidates for treatment with a radical esophagectomy. Results: Twenty-four specimens (11%) had no residual primary cancer (ypT0), 39 (18%) had 1% to 10% residual cancer, 48 (23%) had 11% to 50%, 101 (48%) had more than 50%. Survival was worse with increasing residual primary ESCC, plateauing at 50%. Poorer TRG was associated with worse 3-year overall survival. Better pathologic grade (G), larger number of pack year smoking, fewer cycles of induction chemotherapy, lower level of creatinine, younger age, greater tumor length and clinical T stage were associated with poorer TRG. Conclusions: Better TRG in response to preoperative chemotherapy is associated with a linear increase in survival after esophagectomy for locally advanced ESCC. A nomogram has been developed that can be used to predict TRG. Therefore, for patients with poorer TRG, the role of adjuvant therapy needs to be further assessed in an attempt to improve survival.
The GAIA (CLL13) trial: An international intergroup phase III study for frontline therapy in chronic lymphocytic leukemia (CLL).
Authors: Von Tresckow Julia, Niemann Carsten, Arnon P. Kater, Jasmin Bahlo, Moritz FÃ¼rstenau, Anna-Maria Fink, Michael Gregor, Patrick Thornton, Tamar Tadmor, Kirsten Fischer, Matthias Ritgen, Karl A Kreuzer, Eric Eldering, Stephan Stilgenbauer, Marinus Van Oers, Christian Geisler, Michael J. Hallek, Barbara Eichhorst
Journal: Journal of Clinical Oncology (2018)

TPS7582 Background: Chemoimmunotherapy (CIT) is still standard of care in first line treatment of fit CLL patients (pts) without del(17p) or TP53 mutation. However, CIT is often associated with side effects caused by the general cytotoxicity of chemotherapy. Testing of chemotherapy-free treatment regimens with increased efficacy and superior toxicity profiles including CD20-antibodies and targeted drugs such as venetoclax (Ve) and ibrutinib (I) head to head with CIT is therefore warranted in this pt group. Methods: The trial is an investigator initiated trial of the German CLL Study Group in cooperation with the Nordic CLL Study Group, HOVON, SAKK, Cancer Trials Ireland and the Israeli CLL Study Group. Sponsor of the trial is the University of Cologne. It is registered at www.clinicaltrials.gov as # NCT02950051. 920 pts with a cumulative illness rating scale score ≤ 6 and a creatinine clearance ≥70ml/min who are diagnosed with previously untreated CLL according to iwCLL guidelines without del(17p) or TP53 mutation will be included and 1:1:1:1 randomized into four treatment arms. In the standard arm, six cycles of CIT with fludarabine, cyclophosphamide plus rituximab for pts ≤ 65 years or bendamustine plus rituximab for pts > 65 years are given. In the experimental arms 12 cycles of Ve containing regimes are tested: Ve plus rituximab (RVe), Ve plus obinutuzumab (GVe) and Ve plus ibrutinib and obinutuzumab (GIVe). Two co-primary endpoints were defined: minimal residual disease (MRD) negativity for the comparison of CIT versus GVe and progression free survival (PFS) for the comparison of CIT versus GIVe. Secondary endpoints include comparisons of MRD and PFS for the other treatment arms, overall survival, safety parameters and health-related quality of life. Recruitment started in December 2016 and is estimated to take 33 months (m). The final analysis of the MRD endpoint is expected to be performed 49 m after trial initiation together with the interim PFS analysis. The final analysis of the PFS endpoint is expected to take place after 73 m, which will also be the formal end of trial. After the second meeting of the data safety monitoring board in February 2018 the trial continues recruiting as planned. Clinical trial information: # NCT02950051.
Randomized feasibility study of temozolomide chronotherapy for high grade glioma.
Authors: Jian Li Campian, Grayson Talcott, Melissa Meyer, Emily Slat, Chai Avvaru, Puspanjali Bhatta, Joshua Rubin
Journal: Journal of Clinical Oncology (2018)

e14035 Background: High grade glioma (HGG) (Glioblastoma is the most common type) is the most frequent primary CNS malignancy in adults. Treatment involves maximal safe resection, followed by concurrent radiotherapy with temozolomide (TMZ), and adjuvant TMZ. Unfortunately, the benefits are modest. In addition, side effects from TMZ including myelosuppression and immune suppression can delay therapy. TMZ, however, is the ideal experimental chronotherapeutic. It readily crosses the blood brain barrier and has a short half-life. Thus, the effective intratumoral delivered dose is likely to be substantially modulated by daily variations in systemic metabolism, while cytotoxic effects are likely to vary with intrinsic daily rhythms in processes like DNA damage. Thus, we conducted a pilot study assessing the feasibility and preliminary clinical impact of chronotherapeutically administered TMZ in patients with HGG. Methods: Adult patients ( > 18 years) with HGG (WHO grade III/IV) were eligible. Patients were screened and consented prior to initiation of monthly TMZ therapy. Eligible patients were randomized to take TMZ in the morning (AM) before 10AM or in the evening (PM) after 8PM. Results: At the time of this submission, 27 out of a planned 30 patients have been enrolled with 14 treated in AM and 13 in PM. Our preliminary data indicate that TMZ chronotherapy is feasible. In addition, AM dosing was associated with higher incidence of adverse events (AE), particularly with higher-grade hematologic toxicities (Table 1). Similarly, higher incidence of AEs in other disorders in AM cohort than in PM cohort (data not shown). Table 1. Summary of Hematologic Adverse Events. Clinical trial information: NCT02781792. Conclusions: AM dosing TMZ is associated with higher incidence of AEs. A larger prospective clinical trial to evaluate clinical outcomes with TMZ chronotherapy is warranted in the future. Hematologic Disorders Adverse Event # (%) of patients Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 AM Dosing (N = 14) Thrombocytopenia 1 (7) 1 (7) 1(7) Anemia 4 (29) 1(7) 1(7) Neutropenia 1(7) 1(7) Lymphopenia 3 (21) 1(7) 2(14) PM Dosing (N = 13) Anemia 4 (31) Lymphopenia 2 (15)
Profiling of circulating tumor (ct)-DNA for potentially actionable targets in prostate cancer (PCa).
Authors: Guru Sonpavde, Rebecca J Nagy, Neeraj Agarwal, Theodore Stewart Gourdin, Gurudatta Naik, Shahrooz Eshaghian, Jue Wang, Andrew J. Armstrong, Ulka N. Vaishampayan, Petros Grivas, Sumanta K. Pal, Richard Burnham Lanman, AmirAli Talasaz, Michael B. Lilly
Journal: Journal of Clinical Oncology (2016)

5035 Background: Genomic profiling of metastatic PCa tissue is challenging and circulating tumor cells may not recapitulate entire tumor biology. Cell-free ctDNA is detectable in most patients (pts) with advanced cancer and may capture relevant alterations in cancer cells from different tumor sites. We studied the frequency of ctDNA alterations in potentially actionable genes in pts with PCa. Methods: Patients with PCa that underwent ctDNA analysis using Guardant360 were identified. A 70-gene ctDNA next generation sequencing panel from a CLIA-licensed, CAP-accredited laboratory (Guardant Health, Inc.) was used to sequence all exons in 29 cancer genes, critical exons in 39 genes, and amplifications (16 genes), fusions (6 genes), indels (3 genes), harvested from 10 mL of peripheral blood. Results: We studied 449 pts with PCa (median age 71, range 42-92) with at least one ctDNA test. ctDNA alterations were detectable in 386 patients (84%). Genes with the highest frequency of somatic alteration including amplification (*) in the overall group were: TP53 (54%), AR* (47%), FGFR1/2/3* (20%), MYC* (19%), PIK3CA* (19%), CDK4/6* (16%), EGFR (15%), BRAF *(14%), APC (13%), NF1 and MET (each 12%). A subset of 128 pts with confirmed metastatic castration-resistant prostate cancer (mCRPC) had a similar distribution and frequency of genomic alterations compared to the overall group. Recurrent somatic mutations in AR, PIK3CA, APC and CTNNB1 were identified in the mCRPC cohort at similar frequencies compared to prior studies of tumor tissue analyses. 38 mCPRC pts were confirmed to receive ≥ 4 cycles of 1st or 2nd line taxane chemotherapy and had f/u data; TP53 mutations were associated with longer PFS (PCWG2 criteria; p = 0.032) and PIK3CA mutations were associated with shorter PFS (p = 0.024) following taxane therapy, using a log rank test. Serial ctDNA profiling available in 10 pts revealed clonal evolution of alterations in AR, PIK3CA, BRCA2 and NF1. Conclusions: In this large dataset, ctDNA was frequently detected in pts with PCa with an alteration profile similar to that seen in tumor tissue. ctDNA analysis offers a non-invasive means of serially profiling tumor DNA to identify treatment targets and emerging markers of resistance.
Prevalence and predictors of decreased cardiorespiratory fitness among cancer patients.
Authors: Jesse Pittard Caron, David Payne, Ben Coumbe, Ann Partridge, Anju Nohria, John Groarke
Journal: Journal of Clinical Oncology (2018)

10071 Background: Exercise limitation is prevalent among cancer (CA) patients (pts). Predictors of decreased cardiorespiratory fitness (CRF) in CA pts require investigation. Methods: Single-center retrospective study of 1,632 CA pts (mean age 64 ± 12 years; 58% male, 45% prostate CA; 27% breast CA, 15% Hodgkin lymphoma, 13% head and neck CA) referred for exercise treadmill testing (ETT) a median of 6.8 (3.1, 12.4) years after a CA diagnosis. CRF was determined by peak metabolic equivalents (METs) achieved during ETT. Decreased CRF was defined as failure to achieve > 8 METs. Multivariable logistic regression models assessed associations of CA therapies with decreased CRF. Results: 36.6 % of CA pts had decreased CRF. Any chemotherapy, supra-diaphragmatic radiation therapy (RT), and the combination, were independently associated with a significantly higher likelihood of decreased CRF in an age- and sex-adjusted model (Table). These factors remained significant and anthracycline exposure was associated with a 53% increased risk of decreased CRF in the larger multivariable model. Conclusions: : Decreased CRF is prevalent among CA pts. Exposure to chemotherapy and/or supra-diaphragmatic RT predispose to decreased CRF in this cancer cohort. Interventions to improve CRF should be considered for select CA pts, especially those treated with chemotherapy and/or supra-diaphragmatic RT. Age- and sex-adjusted OR (95% CI), p value Adjusted* OR (95% CI), p value Any chemotherapy (n = 478, 29%) 1.75 (1.33, 2.29), p < 0.0001 1.84 (1.35, 2.52), p = 0.0001 Anthracycline chemotherapy (n = 267, 16%) 1.36 (0.96, 1.92), p = 0.08 1.53 (1.04, 2.27), p = 0.032 Supra-diaphragmatic RT (n = 703, 43%) 1.52 (1.16, 1.98), p = 0.001 1.56 (1.14, 2.11), p = 0.005 Combination of any chemotherapy and supra-diaphragmatic RT (n = 386, 24%) 1.92 (1.43, 2.57), p < 0.0001 1.99 (1.42, 2.81), p < 0.0001 *Adjusted for age, sex, low body mass index, obesity, diabetes mellitus, congestive heart failure, ischemic heart disease, hypertension, smoking history, atrioventricular nodal blocking agents, abnormal heart rate recovery, abnormal blood pressure response to exercise, chronotropic incompetence, positive ETT result, and interval from diagnosis to ETT
Effect of older age and comorbitities on outcomes with neoadjuvant chemotherapy (NAC) for epithelial ovarian cancer (EOC).
Authors: Zhaomin Xu, Carla Francesca Justiniano, Adan Z Becerra, Christopher Thomas Aquina, Francis P. Boscoe, Maria J. Schymura, Fergal J. Fleming, Larissa K. F. Temple, Gary R. Morrow, Lori M. Minasian, Sarah Madhu Temkin
Journal: Journal of Clinical Oncology (2017)

e17101 Background: Although a survival benefit for NAC has not been shown in the overall population of EOC, some patients may benefit from NAC. This analysis evaluates the role of age and comorbidities on the effect of NAC compared to upfront surgery on survival among EOC patients in New York. Methods: Patients who underwent surgery for stage II-IV EOC from 2006-2013 were included from the New York State Cancer Registry and the Statewide Planning and Research Cooperative System. Elderly age was defined as &gt;70 years. Comorbidity burden was defined with the Charlson Comorbidity Index (CCI). Cox models were used to examine the effect of NAC on 5 year overall survival. The analysis was then stratified by age and comorbidity score to evaluate the role of NAC in specific subgroups. Results: 4617 patients met inclusion criteria of which 25% were elderly and 11% received NAC. Factors associated with receipt of NAC included age &gt; 70, advanced stage, serous histology and high hospital volume (p&lt;0.01). After adjustment for patient, hospital, and surgeon characteristics, NAC was associated with a 27% (p&lt;0.01) increase in 5 year overall mortality in all EOC patients. Among the elderly, NAC did not have a significant effect on overall (p=0.47) or EOC-specific survival (p=0.24). Elderly and non-elderly women without comorbidities had a higher risk of death with NAC than primary surgery. There was a trend towards improved survival among elderly patients with higher comorbidity scores. (Table) Conclusions: The impact of NAC on EOC survival differs dependent on age and comorbidities. Patients with no comorbidities may have better prognosis with upfront surgery. Counterintuitively, those with more comorbidities, particularly the elderly, may derive survival benefit from upfront neoadjuvant therapy. [Table: see text]
Abstract 17903: Cardioprotection by Exogenously Administered Endothelial Progenitor Cells (EPCs) After Ischemia-Reperfusion Injury is eNOS Dependent
Authors: Kentaro Jujo, Haruki Sekiguchi, Sol Misener, Ekaterina Klyachko, Joern Tongers, Aiko Ito, Christine Kamide, Ting Liu, Tina Thorne, Gangjian Qin, Douglas W Losordo
Journal: Circulation (2010)

Background: Nitric oxide (NO) production from eNOS protects cardiomyocytes from apoptosis after ischemia-reperfusion (IR) injury. Recent studies suggest that exogenously administered endothelial pr...
Immune-related adverse events to predict survival in patients with advanced non-small cell lung cancer treated with nivolumab: A multicenter analysis.
Authors: Biagio Ricciuti, Andrea De Giglio, Marta Brambilla, Maria Bassanelli, Giulio Metro, Vienna Ludovini, Sara Baglivo, Rita Chiari
Journal: Journal of Clinical Oncology (2018)

9084 Background: Anti-PD1 or anti-PD-L1 are the current standard of care for platinum-pretreated advanced non-small cell lung cancer (NSCLC) patients (pts), having shown to prolong survival as compared to chemotherapy in second line setting. Pts treated with these drugs not infrequently experience the so-called immune-related adverse events (irAEs), which we hypothesize reflect antitumor responses. In this study we investigated whether irAEs were associated with nivolumab efficacy in pts with advanced NSCLC. Methods: We conducted a retrospective study of pts with advanced NSCLC treated with nivolumab between Oct 2013 and Sept 2017. IrAEs were defined as AEs having immunological basis that required monitoring and interventions. We identified two groups according to the development of irAEs and evaluated the ORR, PFS and OS. Results: In a cohort of 127 pts, (median [range] age, 63 [30-81] years; 84 men [66.1%], 43 women [33.9%]; 34 [26.8%] with squamous (Sq) histology, 93 [73.2%] with Nsq histology), irAEs occurred in 57 of 127 study pts (44.8%). Six of them (10.5%) experienced grade 3 or higher irAEs. ORR and DCR were significantly higher in pts with irAEs (68.8% versus 4.8%, P < 0.0001 and, 79.6% versus 20.3% P < 0.0001, respectively). The median PFS was significantly longer in the irAEs group (8.6 [95%CI 4.3-11.7] versus 2.1 [95%CI 1.7-2.4] months, P < 0.001). Median OS was also significantly longer in pts with irAEs (17.4 [95%CI 8-28.8] versus 3.7 months [95%CI 2.7-4.6], P < 0.0001). Importantly, pts with ≥ 2 irAEs had a significantly prolonged OS as compared to those who developed 1 irAE (median NR versus 11.9 months, P = 0.04). Multivariate analysis confirmed that irAEs were significantly associated with improved survival outcomes, with HR of 0.27 (95% CI, 0.17-0.43; P < 0.001) for PFS and 0.36 (95% CI, 0.22 to 0.59; P < 0.001) for OS. Conclusions: In this multicenter study the development of irAEs was a strong predictor of prolonged OS in NSCLC pts treated with nivolumab. Of note, pts who developed ≥ 2 irAEs had a more pronounced survival benefit as compared to pts with only one event. Further studies are required to investigate the molecular mechanisms underlying this association.
Oncological urgent care department: Planning for the unexpected.
Authors: Jessica Livneh, Ofir Morag, Beatrice Shaham, Raanan Berger, Itay Amit, Ella Muller, Einav Nili Gal-Yam
Journal: Journal of Clinical Oncology (2018)

e18772 Background: Oncology treatments have increased in complexity and diversity, contributing to complications and side effects, resulting in need for urgent care. Historically, the response to these urgent situations took place in departments such as Emergency Room or chemotherapy infusion centres. These departments are not designed for these treatments, leading to sub-optimal care. In September 2016, an oncological urgent care department was opened at the Sheba Medical Center. The planning for the new department was done according to the P.D.C.A. Cycle Model. In spite of the careful planning, the reality was much more complex than expected. Methods: P.D.C.A cycle model The Plan–Do–Check–Act cycle is a four–step model for carrying out change. In order to be effective, the PDCA cycle should be repeated for continuous improvement. Plan- lack of designated response for urgent needs of the oncology patients led to gathering information on number of patients; suitable setting and resources. The initial gathering of data resulted in an expected influx of 15 patients per day who were in need of urgent palliative care, such as symptom management, psychosocial support, and dealing with side-effects of cancer treatments. Do- On September first 2016 the unit was opened with the capacity to treat 20 patients a day. Results: Check- The main gap between expectation and reality was a higher patient load than expected, as well as more complex needs. Six months after opening, the average number of patients per day rose to 30. Pleural/ abdominal taps and blood transfusions were performed daily .Repeated cases of clinically unstable patients and immediately terminal patients were but a few of the unexpected challenges. Act- Triage course for nurses, increase manpower, better definition of targeted population, direct contact and referral to the general ER and a new setting for continuing education. Conclusions: Plan – Lessons learned from this pilot has initiated major changes in our oncology unit including a plan to build a specialized oncology urgent unit with appropriate staff, improved setting and resources and to expand this to other patient groups such as haematological patients.