tbuckley/cabot-search huggingface dataset:
Clinical relevance of PD-L1 expression and its relation to tumor-infiltrating lymphocytes in cervical cancer.
Authors: Rafael Grochot, Floriano Riva Neto, Aline Tregnago, Sargeele Silva, Cassiano Scholze, Rui Norris, Debora Weschenfelder, Fabio Pasqualotto, Lessandra Michelim, Andre B. Reiriz, Janaina Brollo
Journal: Journal of Clinical Oncology (2018)

e17511 Background: Cervical cancer is the 4th most common cause of cancer-related deaths in women worldwide. PD-1 is expressed on tumor-infiltrating lymphocytes (TILs) from many different tumor types, as PD-L1 has been reported to be the ligand commonly upregulated in many human cancers, promoting immune evasion by tumor cells, thus providing a good rationale for the development of antitumor therapies targeting this pathway. Our goal was to investigate the prognostic value of PD-L1 expression and TILs in a cohort of cervical cancer patients and their relation to prognostic factors and survival outcomes. Methods: All consecutive patients diagnosed with cervical cancer from a General Hospital in southern Brazil were reviewed through Jan/12-Dez/16. Pretreatment biopsies were assessed for PD-L1 expression and TILs by three independent pathologists. Clinicopathological features and survival endpoints were assessed and correlated to the biomarker findings. Fisher’s exact test, χ2 and Cox regression models were used. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results: The median follow up was 26.2 months. Of 59 patients included, PD-L1 immunohistochemical expression was observed in 32.2%. Among PD-L1 expression cases, 8,5% showed strong-positive staining (>50%). There was no significant association between PD-L1 expression and clinicopathological features. The median PFS was 11,5 months for PD-L1-positive cases and 24,3 months for PD-L1-negative cases (p=0.26). The median OS was 47.8 months for PD-L1 negative patients and not reached for PD-L1-positive cases (p=0.96). Low TILs volumes were observed in 57.6%, moderate in 23.7% and strong in 18,.6% of cases. These different volumes were not significantly associated to clinicopathological features nor survival outcomes. PD-L1 expression was observed in 27.1% of TILs and exerted no statistical impact on OS or PFS. Conclusions: PD-L1 was expressed in a minority of cervical cancer cases and was not related to clinicopathological characteristics nor to survival outcomes in this cohort. In addition, PD-L1 expression in TLIs did not demonstrate statistical significance in cervical cancer patients.
Incidence of treatment effect and characteristic MRI findings in immunotherapy-treated melanoma patients with brain metastases receiving stereotactic radiosurgery.
Authors: Justin Lin Sovich, Ashok Srinivasan, Michelle Miran Kim, Jason Heth, Leslie Anne Fecher, Christopher D. Lao
Journal: Journal of Clinical Oncology (2018)

2066 Background: Melanoma brain metastasis (MBM) treated with stereotactic radiosurgery or stereotactic body radiation therapy (SRS/SBRT) and immunotherapy may have higher rates of treatment-related injury including radiation necrosis, which can be difficult to differentiate from disease progression. Little is known about characteristic radiographic findings to guide decision-making. Methods: We identified all patients (pts) with MBM from the University of Michigan from 2012-2017 who were treated with SRS/SBRT. Pts receiving immunotherapy were compared to those who had not. Overall incidence of treatment-effect (TE) (pathologically confirmed or inferred by > 6 mos stable imaging) were calculated. We reviewed MRIs in pts with TE for conventional metrics including enhancement, T2 hyperintensity, and apparent diffusion coefficient (ADC) and perfusion parameters including calculated blood volume (rBV), blood flow (rBF), time to maximum (tMAX), and leakage (K2). Results: 104 pts received SRS/SBRT and immunotherapy and 29 pts had not. Among the immunotherapy group, 16 had TE (6 pathologically confirmed, 10 by serial imaging) (15.4%). Of the 29 who did not receive immunotherapy, one had TE (pathologically confirmed) (3.45%). The observed risk difference was 12.0% (95% CI 2.4% to 21.6%). We reviewed MR findings for 18 lesions in 15 pts with TE, all of which had enhancement with T2 hyperintensity. Reliable ADC values were calculated for 14 lesions, averaging 112.8 (range 72 to 192). Perfusion imaging was available for 9 lesions, with average rBV 1.63 (range 0.63 to 3.6), rBF 23.86 (9 to 55.4), tMAX 5.71 (0.99 to 27), and K2 -266.78 (-111to -636). Conclusions: SRS/SBRT and immunotherapy resulted in higher absolute risk of treatment-related changes. MRI findings were consistent with existing data on radiation necrosis in glioblastoma multiforme which could help guide decision making in MBM. Comparative analysis on tumor progression in this population is ongoing and will be presented.
Clinical significance of microRNA expression in patients with Epstein-Barr virus associated gastric cancer.
Authors: Byung Woog Kang, Keun Hur, Young Hun Choi, Eun Hye Lee, Jong Gwang Kim, Soo Jung Lee, Jin Ho Baek, An Na Seo
Journal: Journal of Clinical Oncology (2016)

e15563 Background: Previous reports have shown that the expression of miRNA was involved in the development or prognosis of Epstein-Barr virus associated gastric cancer (EBVaGC). Therefore, the expression or target genes of the EBV miRNA can be useful as biomarker for EBVaGC. This study investigated the clinical significance of EBV miRNA expressions in patients with EBVaGC. Methods: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in-situhybridization. Among the 120 patients, the miRNA expression was examined in 39 tumor and 39 paired normal mucosal tissues from available formalin-fixed paraffin embedded tissues. The ebv-miRNAs expression levels for ebv-miR-BART1-5p, ebv-miR-BART4-5p, and ebv-miR-BART20-5p were determined by quantitative real-time PCR and the data were normalized relative to U6 expression. The average value of ebv-miRNAs expression levels was used as the cutoff point. Results: The median age of the patients was 64 years (40-76) and 31 (79.5%) were male. The pathologic stages after surgical resection were as follows: stage I (n = 13), stage II (n = 12), and stage III (n = 14). The expression of these miRNAs was significantly higher in tumor tissue than paired normal tissue (P< 0.001 for each). Of these 39 patients, 14 patients (35.9%), 11 patients (28.2%), and 13 patients (33.3%) were determined as BART1-5p-high expression group, BART4-5p-high expression group, and BART20-5p-high expression group, respectively. In a univariate analysis, BART20-5p were significantly associated with longer recurrence-free survival (RFS)( P= 0.028), yet not overall survival. In a multivariate analysis, BART20-5p expression level has a tendency of favorable outcome indicator for RFS (P= 0.093, HR = 0.219, 95% CI = 0.037-1.290). Conclusions: The ebv-miR-BART1-5p, ebv-miR-BART4-5p, and ebv-miR-BART20-5p were highly expressed in EBVaGC tissues, and the expression level of ebv-miR-BART20-5p may predict RFS for patients with EBVaGC. Further studies are warranted to elucidate the roles of EBV miRNAs in carcinogenesis of EBVaGC, which would be a potential therapeutic target.
Effect of molecular profile in non-small cell lung carcinoma on the development of brain metastases.
Authors: Sarah Turner, Moein Alizadeh, Natasha Leigh, Frances A. Shepherd, Gelareh Zadeh, Normand Laperriere, Barbara-Ann Millar, Mark Bernstein, Phillipe Bedard, Caroline Chung
Journal: Journal of Clinical Oncology (2016)

e20640 Background: Non-Small Cell Lung Cancer (NSCLC) is a heterogenous disease with 44% of pts developing brain metastases (BMs). Molecular Profiling (MP) enables selection of patients for targeted therapy and provides prognostic information. This study aims to investigate the impact of MP on the incidence, presentation and prognosis of brain metastases in patients with NSCLC. Methods: Patients (> 18 years) with NSCLC who enrolled in the IMPACT/COMPACT trial were evaluated in 2 groups evaluated: (1) NSCLC with BMs, (cross referencing with prospective BM database) (2) NSCLC without BMs. The following variables were investigated: Age at diagnosis, Smoking Status, Extracranial Disease Status, Race, Mutations (EGFR, KRAS, TP53, and ALK with tumor profiling using TruSeq Amplification or Sequenom Test), Gender, Histology, and Stage at Diagnosis. Endpoints: BM Yes/No. Logistic regression was used to assess the impact of variables on the occurrence of BMs. Results: A total of 242 pts with NSCLC were identified, of which 88 pts (36%) had BMs. Median age was 62 years (range 18-89 years). Median follow up was 32.5 months (range 0.82–256.9 months). Of all patients, 33.3% of Asian pts had EGFR mutation compared to 18.7% of Caucasian pts (Chi-squared p=0.068). On univariate analysis, pts diagnosed with BMs were more likely to be younger age (p=0.006), be Caucasian (p=0.022), have adenocarcinoma histology (p=0.022), be diagnosed initially with stage IV disease (versus lower stage; p=0.007), and have EGFR mutation (p=0.018). Conclusions: The molecular profile impacts the incidence and timing of brain metastases in patients with NSCLC. Specifically, our study found the following factors were associated with the development of BMs: Age (younger), Race (Caucasian), Tumor stage (advanced), Histology (adenocarcinoma) and EGFR mutation present. Patients with EGFR positive tumors developed BMs slower after their initial lung cancer diagnosis. Development of BMs: Multivariable analysis Variable OR, (95% CI) p value Age (younger) 1.04, (1.01-1.06) 0.007 Race – Caucasian 2.75, (1.25-6.06) 0.007 Stage IV at diagnosis 2.35, (1.33-4.15) 0.003 Mutation - EGFR 2.57, (1.30-5.10) 0.007
Preliminary results from patients with metastatic urothelial carcinoma (UC) in a phase 2 study of JS001, an anti-PD-1 monoclonal antibody.
Authors: Xinan Sheng, Zhihong Chi, Chuanliang Cui, Lu Si, Bixia Tang, Xieqiao Yan, Jun Guo
Journal: Journal of Clinical Oncology (2018)

e16505 Background: Monoclonal antibodies (mAb) against programmed cell death-1 (PD-1) have demonstrated antitumor activity across multiple malignancies. JS001 is a humanized IgG4 mAb against programmed death-1 (PD-1) . Previous phase 1 study show the clinical activity in metastasis urothelial carcinom. This study is a phase 2 study to evaluate the safety and efficacy of JS001 in patients with metastatic urothelial carcinom. Methods: This multi-center, open-label, phase II registration study is designed to evaluate safety and efficacy of JS001 in advanced and metastatic urothelial carcinom patients who have failed systemic treatment. JS001 is given at 3 mg/kg IV Q2W until disease progression or intolerable toxicity. Safety and tolerability was assessed by monitoring adverse events (AEs) and antitumor effects were assessed by RECIST v1.1 criteria and irRECIST criteria. Other objectives include immunogenicity and tumor tissue biomarkers. Results: Enrollment began in May 2017. As of February 10, 2018, 33 patients was enrolled. The most common treatment related AEs were grade 1/2, including ALT increase, hyperglycemia , amylase increase, anemia, AST increase and hypothyroidism.Among 27 evaluable patients, no patient have complete response, 8 patients have partial response, and 13 pts achieve stable disease, for an ORR of 29.6% and a DCR of 77.8%. Conclusions: JS001 might benefit for metastatic urothelial carcinom who have failed systemic treatment. More patients will be enrolled in next year. Clinical trial information: NCT03113266.
The influence of surgical excision on survival in high-risk neuroblastoma revisited after introduction of ch14.18/CHO immunotherapy in the HR-NBL1/SIOPEN trial.
Authors: Keith Holmes, Ulrike Poetschger, Sabine Sarnacki, Tom Monclair, Giovanni Cecchetto, Javier Gomez Chacon, Jacob Stenman, Jean-Marc Joseph, Roberto Luksch, Victoria Castel, Shifra Ash, Vassilios Papadakis, Josef Malis, Walentyna Balwierz, Cormac Owens, Holger N. Lode, Tom Boterberg, Dominique Valteau Couanet, Andrew DJ Pearson, Ruth Lydia Ladenstein
Journal: Journal of Clinical Oncology (2018)

10521 Background: The effect of complete macroscopic excision (CME) of the primary tumour on event free survival (EFS) in high-risk neuroblastoma remains controversial. We therefore investigated the influence of CME in patients enrolled on the HR-NBL1/SIOPEN Trial and compared the effect in the pre immunotherapy era. Methods: Eligibility criteria were: inclusion in HR-NBL1/SIOPEN Trial between 2002-2015, stage 4 disease; completion of Rapid COJEC induction ± 2 courses of TVD; no progression/relapse/death; no prior attempt at resection and complete operation data. Intended therapy following operation comprised: HDT/SCT (BuMel or CEM, after 2011 BuMel), 21Gy radiotherapy to the primary site, 13-cis RA and after 2009 ch14.18/CHO antibody ± IL2 in addition. 1504 patients fulfilled these criteria; 737 were treated prior to ch14.18/CHO availability (2002-2009) and 767 in the immunotherapy era. Median observation time was 4.9 years (0.1-14 years). Results: CME was achieved in 77%, incomplete macroscopic excision (IME) in 21% and 2% were inoperable (0E). Surgical mortality was 0.46% (7/1504). Five year event-free survival (5y-EFS ± standard error) was 39%±2% with CME and 30%±3% with IME or 0E (p = 0.002). The cumulative incidence of local relapse (CILR) was 0.17±0.01 (CME); 0.31±0.03 (IME) and 0.42 ±0.10 (0E) (p < 0.001). 88% of patients received radiotherapy (78% CME; 21% IME and 1% 0E). 5y-EFS for patients with CME who received radiotherapy was 44±2%, but 31±6% without (reasons included very young age and very large primary tumours) (p = 0.013) and 35±3% with less than CME compared to 20±1% without radiotherapy (NS). CILR was 0.14±0.01 in patients with CME who received radiotherapy compared to 0.28±0.06 in patients who did not (p = 0.005). 5y-EFS was significantly higher (42±2%) for patients enrolled after 2009 compared to before (32±2%) (p = 0.000). 5-y EFS for patients after 2009 who achieved CME was 45±2% vs. 36±2% after IME and 26±13% after 0E respectively (p = 0.034); compared to 33±2% vs. 26±4% (IME) and 17±11% (0E) (p = 0.059) prior to 2009. Conclusions: In the immunotherapy era, CME in Stage 4 patients who received local radiotherapy resulted in improved 5-EFS. Clinical trial information: NCT01704716.
Pharmacological management of cancer cachexia: A systematic review.
Authors: Shailesh M Advani, Pragali S. Advani, Helena VonVille, Syed Hasan Raza Jafri
Journal: Journal of Clinical Oncology (2018)

e22169 Background: Cancer cachexia affects many cancer patients, especially in the setting of advanced disease. Despite advancements in treatment strategies, no standard treatment or guidelines exist for management of cachexia for cancer patients. In this systematic review, we provide an update on the pharmacological management of cancer cachexia Methods: We performed literature searches in PubMed, Embase, and Medline to identify clinical trials in cancer cachexia from 2004 to 2016. The date of the last search was July 15, 2016. We identified 4396 abstracts met our selection criteria. Three screeners screened a random selection of abstracts to assess for interrater reliability. Following additional training due to low kappa scores, each screener screened two-thirds of all abstracts, and identified 149 articles for full text review. The final set included 16 articles to be included in the final review. The primary outcome was impact of pharmacological management on weight change in cancer patients. Additional outcomes included impact of physical functioning, QOL, and survival. Results: We identified 16 studies focusing on pharmacological management of cancer cachexia. Agents showing promising results included anamorelin, enorbasm, and combination therapy using megesterole acetate and thalidomide ± nutritional supplements. Anamorelin at 50 or 100 mg for 12 weeks showed a consistent benefit across all studies. Enorbasm at 1 and 3 mg was also effective in managing cachexia. No agents showed functional improvement in cancer patients Conclusions: Despite assessment of several agents, there remains no clear standard of care for the treatment of cancer-associated cachexia. Some agents have shown promising results, but further research is required. More focus on combination approach needs to be emphasized to target underlying mechanisms promoting cancer cachexia.
Discovery of a reliable and robust methylome classifier of HPV driven head and neck cancer with favorable response to chemoradiation: A multicenter study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).
Authors: Bouchra Tawk, Juergen Debus, Christian Schwager, Annett Linge, Ute Ganswindt, Inge Tinhofer, Volker Budach, Martin Stuschke, Panagiotis Balermpas, Franz Rödel, Anca Grosu, Daniel Zips, Stephanie E. Combs, Mechthild Krause, Wilko Weichert, Michael Baumann, Claus Belka, Gerhard Dyckhoff, Christel Herold-Mende, Amir Abdollahi
Journal: Journal of Clinical Oncology (2018)

6019 Background: Human Papilloma Virus (HPV)-driven head and neck cancer (HNSCC) is associated with good prognosis. The prognostic value of HPV-DNA and p16 IHC was recently reported by this consortium. Discordance between HPV and p16 status is consistently observed impacting patient stratification and treatment outcome. We sought to overcome this limitation by developing a next-generation methylome-based classifier of HPV-driven HNSCC. Methods: HPV-DNA and p16 status of a DKTK-ROG multicenter retrospective cohort of patients (n = 194) with oropharynx cancer (OPC), oral cavity- and hypopharynx cancer (non-OPC), homogenously treated with surgery and adjuvant cisplatin-based radiochemotherapy (RCHT), was employed as a training set. Five validation cohorts were utilized including DKTK-ROG patients with definitive RCHT (n = 110), three additional RCHT cohorts from Heidelberg, Dresden, Munich (n = 222) and The Cancer Genome Atlas – HNSCC cohort (TCGA, n = 206). Overall methylome data from 732 samples including two different sources (FFPE/FrFr) and platforms (Illumina 450K and EPIC 850K) were studied. Results: A 24-probe set methylome-based classifier of HPV-driven HNSCC was discovered (HPV-M) to significantly correlate with improved clinical outcomes: HR for local recurrence (range 0.11-0.19), disease progression (range 0.16-0.29) and overall survival (OS, range 0.19-0.42) were significant in all cohorts (p < 0.05). Notably, HPV-M+ classification was superior to HPV-DNA+ status or p16+ IHC in predicting OS in all cohorts independent of tumor localization (OPC/non-OPC). Likewise, HPV-M showed a strong correlation with HPV-DNA and p16 status (p < 0.0001). Across cohorts ~ 10% discordance between HPV-M and HPV-DNA or p16 status was found, respectively. Among these patients (n = 71), OS was significantly reduced in patients with HPV-M negative vs. positive tumors (p < 0.009). Conclusions: We present a novel robust and independent methylome-based classifier of HPV-driven HNSCC that could be instrumental for accurate patient stratification in the era of de-escalation trials.
A new nodal classification based on log odds and location of involved lymph nodes in lung cancer.
Authors: Rui Zhou, Jingwen Zhang, Huiying Sun, Dongqiang Zeng, Wangjun Liao
Journal: Journal of Clinical Oncology (2017)

e20069 Background: To explore the prognostic effect of log odds of positive lymph nodes (LODDS) in node-positive non-small cell lung cancer (NSCLC) patients, and evaluate whether a model incorporates the pN and LODDS is a more reliable prognostic determinant in these patients. Methods: Data of 9557 NSCLC patients (pT1-pT3, pN1-pN2, M0) with lymphadenectomy recorded in the Surveillance Epidemiology and End Results database between 2004 and 2009 were retrospectively studied. Results: In adjusted analyses, LODDS value was an independent prognostic factor for patients with node-positive NSCLC, as well as pN classification and MLN count. However, the LNR value lost its significance in multivariate regression model. Next, we established the pN-LODDS (N-L) classification model and observed that it had better discriminatory ability, monotonicity, and homogeneity for prognostic stratification, as well as more accurate time point OS prediction than either of pN, MLN and LODDS classifications alone. Moreover, besides the pN classification, the N-L model could serve as a referential indicator designing postoperative treatment in node-positive NSCLC patients. Analyses stratified by the N-L classification showed that postoperative radiotherapy was independently linked to prolonged survival in patients with N-L 3 classification, N-L 5 classification, and in pN2 subgroup of N-L 4 classification. Conclusions: Our findings indicated that the N-L classification model could serve as the optimal scheme for prognostic assessment in patients with node-positive NSCLC. Incorporating N-L classification into the staging system will enable clinicians to more accurately predict the prognosis and to guide the decision of regional therapy regiment.
TCT-588 Have patients with a history of cerebral events a higher risk of periprocedural stroke during protected transfemoral aortic valve implantation with use of a double filter cerebral embolic protection device? Results of a large all comers population
Authors: Julia Seeger, Markus Otto, Wolfgang Rottbauer, Jochen Wöhrle
Journal: Journal of the American College of Cardiology (2018)
Safety and clinical activity of durvalumab monotherapy in patients with gastroesophageal cancers.
Authors: Antoine Hollebecque, Zev A. Wainberg, Jaffer A. Ajani, John Marshall, David Cunningham, Sai-Hong Ignatius Ou, Jose Lutzky, Rahima Jamal, Giuseppe Curigliano, Martin Gutierrez, John J. Nemunaitis, Rachel E. Sanborn, Dan Paul Zandberg, Feng Xiao, Natasha Angra, Shaad Essa Abdullah, Neil Howard Segal
Journal: Journal of Clinical Oncology (2018)

4032 Background: PD-(L)1 checkpoint blockade has shown clinical benefits in gastroesophageal (GE) cancers. Durvalumab, a selective, high-affinity, engineered human immunoglobulin G1 anti-PD-(L)1 monoclonal antibody, has demonstrated durable clinical activity and a manageable safety profile in multiple tumor types. Here we present the first report of safety and activity in the GE cohort of the dose-expansion portion of an ongoing Phase I/II, multicenter, open-label study. Methods: Patients with histologically or cytologically confirmed GE cancers received durvalumab 10 mg/kg IV Q2W for 12 months or until unacceptable toxicity or disease progression. The primary objective was safety. A secondary objective was antitumor activity (investigator-assessed by RECIST v1.1). Results: As of Oct 16, 2017, 51 patients received durvalumab with median follow-up of 41.3 months (range, 1.3–49.2). 98% had received prior treatment, including 69% with ≥2 prior therapies (39% with ≥3 prior therapies). 7.8% completed the 12-month treatment period. Treatment-related adverse events (TRAEs) occurred in 56.9% of patients, most commonly fatigue (35.3%), nausea (13.7%), and diarrhea (13.7%). Grade 3–4 TRAEs were reported in 15.7% of patients (none immune-related), most commonly fatigue (11.8%) and vomiting (3.9%). TRAEs led to dose delays or interruptions in 7.8% of patients. There were no serious TRAEs or TRAEs leading to discontinuation or death. Confirmed overall response rate was 3.9% (2 patients; 1 complete response [CR] and 1 partial response [PR], both of which were ongoing at data cutoff; duration of response 9.7+ to 27.0+ months). Disease control rate 24 (CR + PR + stable disease ≥24 weeks) was 11.8% (95% CI, 4.4–23.9) and median time to response was 3.27 months (95% CI, 2.9–3.6). Median PFS was 1.4 months (95% CI, 1.2–2.4) and the 6-month rate was 9.5%; median overall survival was 4.9 months (95% CI, 2.6–9.1) and the 12-month rate was 31.9%. Conclusions: Findings are consistent with earlier reports from this and other studies; durvalumab showed a tolerable safety profile and evidence of antitumor activity in this mostly second line+ cohort of GE cancer patients. Clinical trial information: NCT01693562.