tbuckley/cabot-search huggingface dataset:
TARIBO trial: Cytoreductive nephrectomy in metastatic renal cell carcinoma patients treated with targeted agents.
Authors: Paolo Grassi, Elena Verzoni, Alessandra Bearz, Sergio Bracarda, Marco Bregni, Sebastiano Buti, Saverio Cinieri, Ugo De Giorgi, Giuseppe Fornarini, Luca Galli, Michele Milella, Franco Morelli, Franco Nole, Rodolfo Passalacqua, Roberto Sabbatini, Daniele Santini, Roberto Salvioni, Vera Cappelletti, Raffaele Ratta, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2017)

TPS4601 Background: In the cytokine era cytoreductive nephrectomy (CN) has been shown to increase survival in patients (pts) with metastatic renal cell carcinoma (mRCC). Efficacy of tyrosine kinase inhibitors (TKIs), including first-line sunitinib and pazopanib has been demonstrated. It is unclear if similar survival benefit could be achieved without CN with TKIs since most of pts enrolled into phase III trials had undergone CN. Methods: A total of 270 mRCC pts will be randomized to receiveCN followed by TKIs vs upfront TKIs without CN. Patients will receive pazopanib 800 mg orally daily or sunitinib 50 mg daily, 4 weeks on/ 2 weeks off. The choice of TKI will be done according to investigator’s clinical practice. Primary objective: to compare clinical benefit, as measured by overall survival (OS), provided by CN followed by TKIs vs upfront TKIs in pts with mRCC. Secondary objectives: i) to compare clinical benefit, as measured by progression-free survival (PFS) and response rate (RR) provided by CN followed by TKIs vs upfront TKIs; ii) Safety; iii) Exploratory analyses: evaluation of the predictive role of circulating tumor cells count and circulating tumor DNA at baseline, before and after surgery (in pts undergoing CN), 24 weeks after randomization and at the time of disease progression. Key inclusion criteria: Favorable or intermediate MSKCC or Heng prognostic risk group; histological diagnosis of RCC with a clear-cell component; resectable asymptomatic mRCC with primary tumor in place; up to three different metastatic sites; ≥ 3 metastatic lesions. Key exclusion criteria: Widespread disease ( &gt; or = 4 metastatic organ sites); disease suitable of metastasectomy ( &lt; 3 lesions confined at one organ site). Statistical plan: The sample size was calculated in order to compare 5-year OS between subjects randomized to receive CN followed by TKIs and those randomized to receive upfront TKIs. A total of 191 deaths will yield 80% power to detect a hazard ratio of 1.5 of upfront TKIs vs CN followed by TKIs with an overall type 1 error of 0.05 (two-sided log-rank test). Such a HR corresponds to an increase in the 5-year OS, from an anticipated value of 10% for TKIs to 21.5% for CN followed by TKIs. To date 10/270 pts have been enrolled. Clinical trial information: NCT02535351.
Impact of age on adjuvant chemotherapy after radical resection in patients with non-small cell lung cancer.
Authors: Lu Yang, Xiaoyu Zhai, Sipeng Chen, Ziping Wang
Journal: Journal of Clinical Oncology (2016)

e20008 Background: Adjuvant chemotherapy (ACT) after radical surgery is known to improve the survival of patients with non-small cell lung cancer (NSCLC). However, there are few studies reporting the impact of age on the efficacy of ACT in NSCLC patients. Methods: All patients who received postoperative ACT in the Cancer Hospital of the Chinese Academy of Medical Sciences between 2001 and 2013 with complete records in the database of the hospital and met the inclusion criteria were enrolled in this study for analysis. The primary end point was disease-free survival (DFS) in terms of age. Survival analysis was performed using Kaplan–Meier estimates, log-rank tests and Cox’s proportional hazards regression analysis. Propensity score matching (PSM) was used, and survival analysis of the match data was carried out. Results: Of 1,129 patients with stage IB to stage III NSCLC who underwent radical resection, 929 who met the inclusion criteria were analyzed. Of them, 166 (17.7%) patients were older than 65 years, and the remaining 763 (82.3%) patients were younger than 65 years as the control group. There was no significant difference in DFS between the two age groups before propensity score was matched (665 days [95%CI 579.46, 759.51] vs. 697 days [95%CI 581.55, 812.45], P = 0.807). Furthermore, no significant impact of age on DFS was observed between the PS-matched groups (653 days [95%CI 550.91, 755.09] vs. 706 days [95%CI 585.68, 826.32], P = 0.778). Surprisingly, the result of subgroup study showed that the risk of recurrence was increased in older patients who received postoperative radiotherapy after ACT as compared with younger patients (HR = 2.317, 95%CI 1.101-4.873, P = 0.027). Conclusions: The results suggest that DFS was similar regardless of age of NSCLC patients. Besides, postoperative radiotherapy could probably decrease the survival benefit from postoperative ACT in older patients. ACT should not be withheld from elderly patients. However, post-ACT radiotherapy might be not advised to the elderly NSCLC patients.
Hepatocellular carcinoma with bone metastases: Incidence, prognostic significance and management—Single center experience.
Authors: Ruchi Bhatia, Sravanthi Ravulapati, Alex Befeler, John J. Dombrowski, Sameer D. Gadani, Nishant Poddar
Journal: Journal of Clinical Oncology (2016)

e15632 Background: Hepatocellular carcinoma (HCC) represents one of the most common causes of cancer related deaths worldwide. Bone metastases from HCC are infrequent, with a reported incidence ranging from 3 to 20% with extremely poor prognosis. Spinal metastases from HCC are extremely rare, with a frequency ranging from 0.2% to 2.2% and are associated with significant morbidity and mortality. We present incidence, outcomes, and treatment of patients with bone and more so spinal metastases from HCC identified in the last 10 years. Methods: This is a retrospective analysis at a single tertiary care institution. All patients with bone metastases from HCC between January 2005 to December 2015 were reviewed. Data collected included patient demographics, clinical presentation, location of metastasis, patient management and survival. Results: Out of 1017 patients with HCC over the period of 10 years, 20 patients were found to have bone metastases of which 7 had spinal metastases. 17 (85%) were male, with median age of 58 years at the time of HCC diagnosis. Cirrhosis was attributed to hepatitis C in 11 (55%), hepatitis B in 1 (5%), alcohol in 5 (25%), and NASH in 3 (15%) patients. 16 (80%) were Child-Pugh class A or B with median AFP score of 4,846. Median time to HCC diagnosis post cirrhosis was 737 days, and metastasis post HCC diagnosis was 105 days. Median survival from diagnosis of HCC and metastasis were 205 and 83 days respectively in all patients. Systemic chemotherapy and Sorafenib was used in 6 (30%) patients while 8 (20%) patients received radiation therapy. Among those patients who did not receive therapy, median survival was 42 days. Median survival after diagnosis of metastasis in patients on Sorafenib and radiation were 83 and 59 days respectively. Conclusions: HCC with bone metastases is very aggressive with a low incidence, and optimal treatment strategies are not well defined. Despite its rarity, the spine was the most common site of bone metastases in our patient population. Sorafenib improved median survival even with metastatic HCC. Incidence of bone metastases was much more common in patients with HCC due to hepatitis C than hepatitis B in our center and warrants further study.
Lymph node ratio as a clinical determinant for selecting adjuvant chemotherapy regimen in curative D2 resected gastric cancer.
Authors: Jun-Eul Hwang, Myung Seo Ki, Hyun Jeong Shim, Woo Kyun Bae, Sang-Hee Cho, Ik-Joo Chung
Journal: Journal of Clinical Oncology (2018)

4034 Background: Adjuvant chemotherapy in gastric cancer improves survival outcomes after curative D2 gastrectomy, especially in stage III. We investigated the clinical prognostic significance and usefulness of lymph node ratio (LNR: ratio between metastatic lymph nodes and examined lymph nodes) for selecting adjuvant chemotherapy regimen in D2 resected stage II/III gastric cancer. Methods: We reviewed the data of 741 patients who underwent curative D2 gastrectomy and received adjuvant chemotherapy. 275 patients received platinum-based chemotherapy, and 466 received TS-1 including oral 5-fluorouracil. The disease-free survival (DFS) was evaluated for the influence of LNR on the clinical outcomes, and the patients were categorized initially into 4 groups, according to LNR (0, > 0-0.1, > 0.1-025, > 0.25), then group 0 and > 0-0.1 were merged because of similar DFS of two groups (0-0.1, > 0.1-0.25, > 0.25). Results: The patients were well discriminated according to LNR irrespective of the adjuvant chemotherapy regimen and stage. On multivariate analysis, LNR was most potent independent prognostic factor for DFS (hazard ratio 2.589, 95% confidence interval 1.874-3.576, P < 0.001). Platinum-based chemotherapy improved 3-year DFS compared with oral regimen (TS-1+oral 5-fluorouracil) in stage III and LNR > 0.25 (P = 0.026). LNR > 0.1 is the discriminant factor that favor platinum-base adjuvant chemotherapy in patients with combined stage III and lymphovascular invasion positivity (P = 0.037, platinum vs. oral regimen, median DFS: 46.867 vs. 21.767 months). Conclusions: The LNR has an important clinical prognostic significance, and the easily identifiable clinical determinant for selecting adjuvant chemotherapy regimen in gastric cancer patients underwent curative D2 resection, especially in stage III gastric cancer.
Novel biomarkers for immunotherapy: from the results of phase I and II study of five therapeutic peptides for advanced colorectal cancer.
Authors: Shoichi Hazama, Norihiro Tanaka, Yuka Inoue, Shinsuke Kanekiyo, Yoshitaro Shindo, Nobuaki Suzuki, Shigeru Takeda, Tomio Ueno, Shigeru Yamamoto, Shigefumi Yoshino, Yusuke Nakamura, Fumiaki Sugiura, Kiyotaka Okuno, Tomonobu Fujita, Yutaka Kawakami, Hiroaki Nagano
Journal: Journal of Clinical Oncology (2016)

e14507 Background: Biomarkers to predict the efficacy of immunotherapy have been awaited. A phase I/II study of five therapeutic epitope-peptides for advanced colorectal cancer (CRC) using five novel HLA-A*2402-binding peptides. We explored the predictive biomarker for the response to immunotherapy. Methods: Each of the five peptides(3mg) was mixed with IFA and subcutaneously administered weekly for 12 weeks and after then biweekly. In the phase II study, chemotherapy was performed simultaneously as mFOLFOX6 (n = 93) or XELOX (n = 3) with bevacizumab (n = 5). All enrolled pts had received the therapy without knowing HLA-A status double-blindly, and the HLA-A genotypes were key-opened at analysis point. Pretreatment serum IL-6, CRP, lymphocyte%, neutrophil/lymphocyte (N/L) ratio ,and expression profiles of miR of the tumor and stroma using laser capture microdissection were evaluated between HLA-A*2402 positive group and negative group. Results: IL-6 < 1.0 (pg/ml) and Lymphocyte% > 15% were the significant predictive markers (p = 0.007, 0.034) for the long survival, which was observed only in HLA-A*2402 positive group. In the patients with IL-6 < 1.0 or lymphocyte% > 15, obvious trend to long survival in HLA-A*2402 positive group was observed. miR-378a of cancer and miR-125b in stromal were confirmed for the predictive biomarkers. Patients with low miR-378a or low miR-125b were significantly survived longer than high miR groups which significances were observer only in HLA-A*2402 group. Conclusions: IL-6, Lymphocyte%, and miRs expression were the predictive biomarkers for the response to peptides vaccine and the selection of patients.
Using clinical pathways to understand biomarker testing patterns.
Authors: Peter G. Ellis, Kathleen Lokay, Amanda Barry
Journal: Journal of Clinical Oncology (2017)

e18189 Background: Via Pathways’ Disease Committees incorporate biomarker testing recommendations into the pathway decision support when the literature supports improved outcome. For several years, the non-small cell lung pathway (NSCLP) has recommended testing for ALK, EGFR, and, more recently ROS1 targeted therapies. The decision support software (VP) requires the practitioner to register testing and results, including the decision not to test. Methods: For the twenty months ending 10/31/16, we analyzed all NSCLP patients treated at UPMC CancerCenter locations for first line, metastatic, non-squamous lung cancer per the VP. Results were analyzed in total and by type of provider (83 community providers vs. 3 academic providers who specialize in lung cancer). Provider’s answers to the biomarker testing question included “positive” results, “negative” results, “test pending”, and “not tested”. Results: Of the 684 treatment starts in the 1 st line non-squamous NSCLP, 100 were patients of academic providers (AP) and 584 were patients of community providers (CP). AP indicated testing for ALK and EGFR in 100% of patients (n=100). CP indicated testing for ALK in 91% (n=532) and for EGFR in 92% (n=538). AP indicated testing for ROS1 in 96% (n=93) and CP indicated testing for ROS1 in 81% (n=473). Results are summarized in the table. Conclusions: Data from clinical pathways software can be utilized to understand biomarker testing rates among providers. In this example, the three AP tested for actionable mutations more frequently than the 83 CP, although both rates of testing appeared to be high. This data can be used to generate hypothesis about patterns of care that may include patient parameters, size of network or other factors that can then further analyzed and tested. Pathways serves as an important tool in promoting and monitoring quality care. [Table: see text]
Genetic analysis of diffuse large B-cell lymphoma occurring in cases with antecedent Waldenström macroglobulinaemia.
Authors: Dipti Talaulikar, Amber Biscoe, Jun Hee Lim, John Gibson, Christopher Arthur, Naomi Mackinlay, Kartik Saxena, Yuen Yee Cheng, Vivien Chen
Journal: Journal of Clinical Oncology (2018)

e19544 Background: Diffuse large B-cell lymphoma (DLBCL) has been reported to occur in 2-10% of cases with antecedent Waldenström Macroglobulinaemia (WM), a low-grade lymphoma characterised by the presence of the MYD88 L265P mutation. This is reported to occur after treatments including Rituximab, alkylating agents, nucleoside analogues and proteasome inhibitors. We report the first case of DLBCL (occurring in the CNS) in a WM patient compliant with and responding to the Bruton’s tyrosine kinase inhibitor, Ibrutinib. Given the lack of understanding of the clonal relationship of DLBCL with antecedent WM, we also aimed to investigate a series of 4 cases with MYD88 L265P and immunoglobulin heavy chain (IgHv) analysis. Methods: DNA was extracted and MYD88 L265P and IgHv were analysed by PCR and sequencing from paired WM and subsequent DLBCL samples of 4 patients (males, age range: 61-89 years). Time to occurrence of DLBCL was 1.5-9 years, and prior treatments included no treatment (patient 3), nucleoside analogues, alkylating agents and Ibrutinib (patient 1). The minimal amount of brain tissue available on Patient 1 was subjected to laser-capture microdissection, IgHv PCR and cloning into TOPO2.1 expression vector prior to sequencing. Results: MYD88 L265P mutation was detected in all 4 cases at diagnosis of WM, and in 3 of the 4 cases at occurrence of DLBCL. The patient with wildtype MYD88 L265P DLBCL had a different IgHv to the treatment naïve WM clone (patient 3), indicating independent clonal origin. Patients 2 and 4 had the same IgHV sequence, indicating clonal evolution from the antecedent WM. The minimal amount of brain tissue available on Patient 1 failed to show a monoclonal band. Thus, it was not possible to determine whether this was a new MYD88 positive CNS DLBCL, or whether it arose from the previous WM. Conclusions: Our data demonstrates that WM patients compliant with and responding to Ibrutinib can develop DLBCL within the CNS despite its known CNS penetrating effects. DLBCL occurring in cases with antecedent WM may evolve from the WM clone or independent to it. Further studies are required to determine whether treatment causes large cell transformation in WM.
Activity of ramucirumab (R) with pembrolizumab (P) by PD-L1 expression in advanced solid tumors: Phase 1a/b study in later lines of therapy.
Authors: Roy S. Herbst, Ian Chau, Daniel Peter Petrylak, Hendrik-Tobias Arkenau, Johanna C. Bendell, Rafael Santana-Davila, Emiliano Calvo, Nicolas Penel, Juan Martin-Liberal, Andres O. Soriano, Philippe Alexandre Cassier, Matthew Krebs, Nicolas Isambert, Ryan Widau, Gu Mi, Jin Jin, David Raymond Ferry, Charles S. Fuchs, Luis G. Paz-Ares
Journal: Journal of Clinical Oncology (2018)

3059 Background: R (anti-VEGFR2) and P (anti-PD-1) are active in patients (pts) with previously-treated non-small cell lung carcinoma (NSCLC), gastric or gastroesophageal adenocarcinoma (G/GEJ) and urothelial carcinoma (UC). Because PD-L1 expression may be a predictive biomarker, we examined the effect of R + P in relation to PD-L1. Methods: Eligible pts had progressive advanced or metastatic G/GEJ, NSCLC and UC, ECOG PS 0-1, and baseline tumor tissue. PD-L1 was assessed using the PD-L1 IHC 22C3 pharmDx assay, where the number of stained tumor cells (tumor proportion score; TPS) or tumor and immune cells (combined positive score; CPS) is relative to total tumor cells. PD-L1 positivity was defined by CPS ≥1% in G/GEJ and UC, and defined by TPS ≥1% in NSCLC. Primary objective was safety and tolerability of R + P. Results: As of 31-July-2017, 92 pts received P 200 mg on Day 1 q3W with R at 10 mg/kg on Day 1 (G/GEJ, n = 17; NSCLC, n = 27; and UC, n = 24) or R at 8 mg/kg, Day 1 and 8 q3W (G/GEJ, n = 24). Baseline demographics and characteristics were as expected for an advanced, previously treated population. Median follow-up duration for G/GEJ, NSCLC, and UC, was 17.9 months (mo), 20.1 mo, and 17.5 mo, respectively. The safety profile was consistent with that of each individual drug, with no additive toxicities. 84 (91%) of 92 pts were evaluable for PD-L1. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) by PD-L1 are shown in the table. 13 pts remained on study treatment (G/GEJ, n = 4; NSCLC, n = 8; and UC, n = 1). Clinical trial information: NCT02443324. NR = not reached Conclusions: In previously treated G/GEJ, NSCLC, and UC, R + P appears to provide more benefit in PD-L1 positive compared to PD-L1 negative pts. Randomized trials are warranted. Updated safety and efficacy results will be presented at the meeting. PD-L1 status G/GEJ (2nd-3rd line) NSCLC (2nd-4th line) UC (2nd-4th line) < 1% n = 17 ≥1% n = 22 < 1% n = 11 ≥1% n = 11 < 1% n = 11 ≥1% n = 12 ORR, n (%) 1 (6) 2 (9) 2 (18) 5 (45) 0 3 (25) PFS, mo (95% CI) 1.9 (1.3-4.0) 4.6 (2.3-8.5) 9.7 (2.1-13.9) 6.9 (2.8-NR) 1.3 (0.4-1.9) 2.5 (1.2-7.4) OS, mo (95% CI) 5.2 (1.7-9.7) 14.9 (4.6-NR) 17.0 (10.5-NR) NR (4.0-NR) 4.8 (0.6-13.9) 6.4 (2.5-NR)
Cost of surveillance imaging in head and neck cancer patients treated with definitive radiotherapy.
Authors: Sweet Ping Ng, Mona K Jomaa, Courtney Pollard, Zeina Ayoub, Abdallah Mohamed, Adam S. Garden, Joel Berends, Gary Brandon Gunn, Steven J. Frank, Heath Devin Skinner, Jack Phan, David Ira Rosenthal, William H. Morrison, Jason Michael Johnson, Erich M. Sturgis, Stephen Yenzen Lai, Clifton David Fuller
Journal: Journal of Clinical Oncology (2017)

6610 Background: The goal of surveillance is to detect potentially salvageable recurrence, allowing early salvage treatment and thereby improving clinical outcomes. Currently, there is limited data on the optimal frequency of imaging for head and neck cancer patients treated with definitive radiotherapy. This study aims to evaluate the cost-effectiveness of surveillance imaging in this group of patients. Methods: Eligible patients included those with a demonstrable disease free interval (≥ 1 follow up scan without evidence of disease and a subsequent visit/scan) treated between 2000-2010. Age, tumor site and stage, induction chemotherapy use, dose/ fractionation, mode of detection of recurrence, salvage therapy, number and modality of scans were recorded. Deaths from disease recurrence or from other causes were also recorded. Imaging costs were calculated based on the 2016 Medicare fee schedule. Results: 1508 patients were included. Mean age was 55.8 years (range: 17-87). Median overall survival was 99 months (range: 6-199). Mean imaging follow up period was 70 months. 190 (12.6%) patients had disease recurrence – 107 locoregional (LR) and 83 distant. 119 (62.6%) of the relapsed group were symptomatic and/or had an adverse clinical finding associated with recurrence. 80.4% of LR relapses presented with a clinical finding, while 60.2% of distant relapses were detected via imaging alone in asymptomatic patients. There was no difference between the successful salvage rates and overall survival between those with relapses detected clinically or via imaging alone. 70% of relapses occurred within the first 2 years post-treatment. In those who relapsed after 2 years, the median time to relapse was 51 months (2 LR and 11 distant relapses). After 2 years, the average cost for detecting a salvageable recurrence for image-detected group was $741 447.41, and the cost for preventing 1 recurrence-related death for image-detected disease was $889 736.89. The number of scans required to detect a salvageable recurrence in an asymptomatic patient after 2 years was 3512. Conclusions: Surveillance imaging in asymptomatic patients without clinically suspicious findings beyond 2 years requires judicious consideration.
TCT-808 Comparison between Clopidogrel and the New Oral P2Y12 Inhibitors in the Treatment of Patients With STEMI Undergoing Primary Percutaneous Coronary Intervention
Authors: Martino Pepe, Annagrazia Cecere, Osvaldo Burattini, Luca Amato, Alessandro Bortone, Emanuela De Cillis, Alessandro Cafaro, Nicola Forzati, Francesco Giardinelli, Stefano Favale
Journal: Journal of the American College of Cardiology (2018)