tbuckley/cabot-search huggingface dataset:
Single institution experience on papillary renal cell carcinoma PD-1/PD-L1 expression, pathological analysis, and outcomes after nephrectomy.
Authors: Bradley Curtis Carthon, Manal Tabba, Wayne Harris, Omer Kucuk, Viraj A. Master, Kenneth Ogan, Adeboye O. Osunkoya, Carla Ellis
Journal: Journal of Clinical Oncology (2017)

e16048 Background: The PD-1/PD-L1 pathway plays an important role in tumor growth and tolerance among renal cancer cells. Renal cell carcinoma (RCC) consists of several different histological subtypes, including clear cell and non-clear cell varieties. Papillary RCC is the most common non-clear cell type and accounts for almost 13% of RCC cases. Our center has a large volume of papillary RCC patients treated by nephrectomy or with systemic therapy. This retrospective study examines pathological criteria, outcomes, and PD-1/PD-L1 expression in a defined cohort. Methods: Institutional review board (IRB) approval was obtained to access and retrospectively review clinical and pathological data of patients that presented with papillary RCC and had a partial or radial nephrectomy during a 1 year duration at our institution. We collected data on survival, systemic treatments, and pathological staging. Tumor samples from the patients were also stained and analyzed for PD-1 and PD-L1 expression. Results: 31 patients were identified with papillary histology after nephrectomy. 45% (14/31) of the patients underwent a radial nephrectomy while 55% (17/31) underwent a partial nephrectomy. Of these 31 patients, 23 had tumor slides available for staining and review. 65% (15/23) of the tumor samples were type 1 papillary RCC, and 35% (8/23) were type 2. PD-L1 was expressed in 13% (3/23) of the cases and PD-1 was expressed in 52% (12/23) of the cases. 71% of the patients were pT1 and 84% of the patients were alive at 5 years. Only 1/31 patients required use of systemic therapy. 74% (17/23) of patients were African American. Conclusions: Patients undergoing nephrectomy for papillary RCC at our institution commonly had small primary tumors with excellent survival. 46% of the tumors expressed PD-1, whereas only 12% expressed PD-L1. Trials that study the inhibition of the PD-1/ PD-L1 pathway may be helpful in strategies for treating both localized and metastatic papillary RCC. Further genomic and pathological examination of additional samples is currently underway.
A phase II study of apatinib on reversing resistance of paclitaxel-containing regimens in advanced gastric cancer (AGC).
Authors: Rongbo Lin, Hui Li, Jie Liu, Shen Zhao, Jiaqing Yu, Nanfeng Fan
Journal: Journal of Clinical Oncology (2018)

e16055 Background: Preclinical study has showed apatinib, an inhibitor of VEGFR-2, could reverse ABC-mediated multidrug resistance by downregulating ABC expression [Zhu, J, et al. 2017 WCLC]. Our preliminary clinical study showed apatinib might reverse resistance to paclitaxel-containing regimens in advanced or metastatic gastric cancer. Herein, the results were updated (Ahead-G323; ClinicalTrials.gov: NCT02697838). Methods: Locally advanced or metastatic gastric adenocarcinoma pts resistant to paclitaxel-containing regimens (disease progression during or within 3 months after chemotherapy) and had measurable lesions were enrolled, and received apatinib (850 mg or 750 mg, po, qd) combined with paclitaxel alone (80 mg/m2, d1, d8, and d15; q4w), POF (paclitaxel 135 mg/m2, oxaliplatin 85 mg/m2, and leucovorin 400 mg/m2, d1; 5-FU 2400 mg/m2 for 46 h; q2w) or other paclitaxel-containing regimen according to ECOG performance status (PS) and drug resistance profile of pts. The primary endpoint was disease control rate (DCR). Results: Twenty-seven pts were enrolled. The baseline characteristics of these pts were: median age 54 (range, 31 to 68) years, male/female 64.0/36.0%, ECOG PS 0/1/2 32.0/64.0/4.0%, having received one/two/three/four lines of prior chemotherapy 25.9/40.7/25.9/7.4%. Among 21 evaluable pts, 4 achieved partial response, 12 achieved stable disease and 5 got progressive disease. The best objective response rate and DCR were 19% and 76.2%. As of Dec 5, 2017, 11 pts were still alive. Moreover, the most common adverse events were anemia (56.5%), neutropenia (56.5%), leukopenia (47.8%), hypoproteinemia (47.8%), hypertension (34.8%), fatigue (34.8%), elevated bilirubin (26.1%), abdominal pain (26.1%), diarrhea (21.7%), and proteinuria (21.7%). Conclusions: This study demonstrated that apatinib may effectively reverse paclitaxel-containing regimen resistance in advanced or metastatic gastric cancer with manageable toxicities. Clinical trial information: NCT02697838.
Measurement of spatial and antibody-based PD-L1 heterogeneity in non-small cell lung cancer.
Authors: Patricia Gaule, Jamaal Rehman, James William Smithy, Maria Toki, Gang Han, Veronique Neumeister, Daniel E. Carvajal-Hausdorf, Kurt Alex Schalper, Vasiliki Pelekanou, Brad Wasserman, Roy S. Herbst, David L. Rimm
Journal: Journal of Clinical Oncology (2016)

9040 Background: Assessment of PD-L1 is not yet standardized and is based largely on “assay performance” rather than protein measurement; with each assay requiring its own specialized platform and antibody. Here we focus on PD-L1 measurement using five monoclonal antibody clones (SP142, E1L3N, 9A11, SP263 and 28-8). We analyzed concordance between antibodies and then determined the heterogeneity between readers and tissue samples. Methods: We designed a PD-L1 index tissue microarray including 30 NSCLC cases with full dynamic range of PD-L1 expression, tissue and cell line controls. The concordance between the antibodies was assessed using diaminobenzidine (DAB) and quantitative immunofluorescence (QIF). Additionally, the correlation among 5 pathologists was assessed on 35 cases of resected NSCLC using SP142 DAB-stained samples on 3 blocks from the same tumor from each case. Results: Correlations between the antibodies ranged predominantly from 0.8-0.9 for tumor cores and 0.83-0.97 (R2) for cell line cores. The 28-8 antibody was excluded due to lack of reproducibility. Among the 5 pathologists a 93.2% intra-class correlation coefficient (ICC) was seen using the percent of tumor cells with membrane or cytoplasmic signal from DAB staining while the ICC was only 19.5% for immune cell staining. The ICC for tumor staining between the 3 blocks of each cases was 93.7% while the ICC between blocks for immune cell staining was 77.7%. A mixed effects model for the QIF assessment of PD-L1 tumor expression showed that the variance between fields of view accounted for 88% of total variance while the variance between blocks only represents 12%. Conclusions: Detection of PD-L1 by a range of antibodies shows high level concordance, suggesting that differences seen in expression is not attributable to the antibodies used. Heterogeneity studies showed that the variance seen is largely between fields of view within the area of the tumor block and that the block to block variance is low (12%). This data suggests that assays that measuring PD-L1 using different antibodies from different regions of patient tumors are likely to be concordant, while demonstrating the microscopic (field to field) appearance of heterogeneity.
Retrospective review of immune checkpoint inhibitor therapy (ICI) at the Michael E. DeBakey VA Medical Center Cancer Center (MEDVAMCCC).
Authors: Jan Ole Kemnade, Nan Chen, John Mbue, Rosetta Lee, Cheng-Yen Chang, Anita Lyn Sabichi
Journal: Journal of Clinical Oncology (2018)

e15091 Background: Given the recent clinical introduction of ICIs, their application, efficacy, predictive markers, and adverse effects are actively being elucidated. Here we describe the use, response, toxicity, and predictive value of patient characteristics in relation to ICIs at the MEDVAMCCC. Methods: A retrospective review was performed on all MEDVAMCCC patients receiving nivolumab (N), pembrolizumab (P) or ipilimumab (I) from 1/2014 to 2/2018. Demographics, comorbidities, social history, medications, cancer type, stage at treatment, prior therapy, and ICI treatment response and toxicity were procured. In addition to descriptive summation, data were analyzed for predictive correlation to treatment response using chi-square test. Results: 91 patients across 11 cancer types were treated with ICI (N:61, P:20, I:4; N or P +I:6). ~50% had non-small cell lung cancer, ~20% melanoma, and ~15% renal cell carcinoma. Other cancers included head and neck, transitional cell and papillary urothelial, hepatocellular, neuroendocrine, renal squamous cell carcinoma (SCC), and urothelial SCC. Stage IV disease was most common (n = 79). Few had stage III (n = 8) or stage II (n = 4) disease. Overall response rate (complete response (CR), partial response (PR), or stable disease (SD)) was 53% (41/79, 12 censored - no restaging yet). 57% developed toxicity (majority grade 1 or 2 with only two grade 4 events). Patients exhibiting two or more toxicities were more likely to respond than those with one or no toxicity (p = 0.007). BMI ≥ 25 was predictive of a higher likelihood of response (p = 0.007). However, exposure to radiation therapy (XRT) at any time as well as smoking status did not predict response. Conclusions: ICI therapy is employed across a multitude of cancers at the MEDVAMCCC. CRs were infrequent (n = 7) but given the patients' advanced stage and prior treatment failures, any CR is significant. Toxicity and BMI ≥ 25 appeared to be predictive of treatment response in this population while XRT and smoking were not observed to be predictive factors. Further observation of this growing dataset should enable us to better characterize ICI therapy leading to more precise application and improved outcomes.
Assessing the difference in efficacy and effectiveness of cancer systemic treatment (tx): A comparison of clinical trial (CT) overall survival (OS) and toxicity data with population-based, real world (RW) OS data.
Authors: Cameron Phillips, Helen Guo, Deborah Schwartz, Wanrudee Isaranuwatchai, Jaclyn Marie Beca, Wei Fang Dai, Jessica Arias, Scott Gavura, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2018)

6581 Background: Often, when counseling patients on therapy, we utilize CT survival and toxicity data to help inform decision-making. While it is commonly believed CT data, derived from highly selected patients (pts), overestimates OS and underestimates toxicity compared with unselected patients in the RW, less is known about how often this occurs and the magnitude of this difference. We aim to quantify systematically the magnitude of OS and toxicity differences between CTs and population-based RW involving contemporary cancer systemic txs. Methods: All pts receiving IV cancer drugs with palliative intent indications that were first funded in Jan 2008 – Mar 2017 under Cancer Care Ontario’s New Drug Funding Program (NDFP) were identified. A literature search was performed to identify landmark CTs with established OS efficacy data (e.g. median OS, 1-year OS rate or Kaplan-Meier OS curves) for each drug indication. Serious adverse event (SAE) rates were collected. Drug indications were included if the public funding criteria matched the CTs’ eligibility criteria. RW OS and hospitalization (H) rates during treatment were ascertained by linking NDFP data to other population-based databases with end of follow-up at May 31, 2017. Results: 32 indications from 21 drugs (9 chemotherapy, 10 targeted therapies, 2 immunotherapy) involving 8,344 CT pts and 29,424 RW pts were included. 29 indications (91%) showed worse OS in the RW when compared to CTs with a median median OS difference of 4.4 months (IQR: 3.2-10.0) and a median 1-year OS difference of 12% (IQR: 8%-21%). Drugs used in the last-line setting had worse OS difference at 1-year (22% vs. 11%). The median difference between RW H and CT SAEs was 12% (IQR: 6%-21%). Conclusions: In most cases, substantially worse OS and greater toxicity were observed in the RW compared to CTs. This study has established a catalogue of population-based OS and H for pts receiving contemporary cancer systemic txs, and provides more relevant information for health-care providers when counseling pts on survival expectations prior to the initiation of systemic txs in the real world.
Subsequent cancers in the long term survivors of Hodgkin’s lymphoma: A SEER based analysis.
Authors: Prabhsimranjot Singh, Vivek Kumar, Neha Chaudhary, Parita Soni, Abhinav Binod Chandra
Journal: Journal of Clinical Oncology (2016)

e19014 Background: The impact of newer radiotherapy techniques and non-alkylating agent based regimens (ABVD and Stanford V) on subsequent cancers in Hodgkin’s lymphoma (HL) survivors remains unclear. Recently a study conducted outside United States (US) reported no change in the risk. This study aimed to compare the rate of subsequent cancers in the HL survivors in US with the general population and to compare the rates in survivors diagnosed before and after the introduction of newer treatment modalities. Methods: The HL patients diagnosed in 1973-1992 and survived beyond 5 years were identified in the Surveillance, Epidemiology and End results (SEER) database. We compared the risk of subsequent cancers with the risk expected in general population and compared the incidence rates in survivors diagnosed in 1973-82 and 1983-92. Results: With a follow-up of 8,662 HL survivors for 151,443 person-years (PY), 2068 subsequent cancers were diagnosed, with standardized incidence ratio (SIR) of 2.53 (95% CI, 2.42-2.64). Lung (SIR 3.80; CI 3.43-4.21) and female breast cancers (SIR 3.45; CI 3.12-3.8) were the commonest. The risk was increased for all cancer types with the highest risk for tumors of salivary gland (SIR 11.68; CI 7.56-17.25), acute myeloid leukemia (AML) (SIR 10.76; CI 7.56-17.25), soft tissue including heart (SIR 9.45; CI 6.92-12.6), non-Hodgkin’s lymphoma (NHL) (SIR 5.02; CI 4.29-5.84) and thyroid (SIR 4.58; CI 3.68-5.65). The risk was highest 15-20 years after diagnosis (SIR, 2.68; CI, 2.51 to 2.87). In the cohort diagnosed in 1973-82, 1111 cancers were diagnosed in 3994 patients (SIR 2.76; 2.6-2.93) while 957 cancers were diagnosed in 5220 patients (SIR 2.27; 2.13-2.42) diagnosed in 1983-92 (P = 0.03). The incidence of thyroid cancers (p = .14), leukemia (p = .46) and NHL (p = .22) was not different. Conclusions: The incidence of subsequent cancers in HL survivors diagnosed after introduction of newer treatment modalities (1983-92) has declined significantly in US. However risk of subsequent hematological malignancies remains unchanged. The risk of secondary cancers is still higher than general population and is maximum 15-20 years after diagnosis. Thus close follow up with active surveillance is crucial for the HL survivors.
Circulating interleukin-18 (IL-18) as a predictor of response to gemcitabine based chemotherapy in patients with pancreatic adenocarcinoma.
Authors: Cigdem Usul Afsar, Mehmet Karabulut, Senem Karabulut, Savas Tuna, Halil Alis, Murat Gonenc, Nergiz Dagoglu, Elif Bilgin, Faruk Tas
Journal: Journal of Clinical Oncology (2016)

e15678 Background: This study was conducted to investigate the serum levels of inteleukin-18 (IL-18) in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters. Methods: Thirty-three patients with PA were investigated. Serum samples were obtained on first admission before treatment was given and during the follow-up period. Serum IL-18 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 30 healthy controls were included in the analysis. Results: The median age at diagnosis was 59 years, range 32–84 years; 20 (61%) patients were men and the remaining were women. Tumor localization was the head of pancreas in 21 (63%) patients. The most common metastatic site was liver in 23 patients with metastasis (n = 19, 83%). The median follow-up time was 26.0 weeks (range: 1.0 - 184.0 weeks). At the end of the observation period, thirty-two patients (97%) were dead. Thirty-nine percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx–responsive. Median overall survival of the whole group were 41.3 ± 8.3 weeks [95% confidence interval (CI) = 25-58 weeks]. The baseline serum IL-18 levels were significantly higher in patients with PA than in the control group (p < 0.001). Serum IL-18 levels were significantly higher in the patients with high erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) (p = 0.01 and p = 0.05) (Table 1). Moreover, the CTx-unresponsive patients had higher serum IL-18 levels compared to CTx -responsive (p = 0.04) ones (Table 1). Conversely, serum IL-18 concentration was found to have no prognostic role on survival (p = 0.45). Conclusions: Serum levels of IL-18 can be a good diagnostic and predictive marker; especially for predicting the response to gemcitabine based CTx in patients with PA but it has no prognostic role.
Galectin-9 is an easy to measure biomarker for the interferon signature in systemic lupus erythematosus and antiphospholipid syndrome
Authors: Lucas L van den Hoogen, Joël A G van Roon, Jorre S Mertens, Judith Wienke, Ana Pinheiro Lopes, Wilco de Jager, Marzia Rossato, Aridaman Pandit, Catharina G K Wichers, Femke van Wijk, Ruth D E Fritsch-Stork, Timothy R D J Radstake
Journal: Annals of the Rheumatic Diseases (2018)

The interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic target. Quantification of the IFN signature is currently performed by gene expression analysis, limiting its current applicability in clinical practice. Therefore, the objective of this study was to establish an easy to measure biomarker for the IFN signature.Serum levels of galectin-9, CXCL-10 (IP-10) and tumour necrosis factor receptor type II (TNF-RII) were measured in patients with SLE, SLE+APS and primary APS (PAPS) and healthy controls (n=148) after an initial screening of serum analytes in a smaller cohort (n=43). Analytes were correlated to measures of disease activity and the IFN signature. The performance of galectin-9, CXCL-10 and TNF-RII as biomarkers to detect the IFN signature was assessed by receiver operating characteristic curves.Galectin-9, CXCL-10 and TNF-RII were elevated in patients with SLE, SLE+APS and PAPS (p<0.05) and correlated with disease activity and tissue factor expression. Galectin-9 correlated stronger than CXCL-10 or TNF-RII with the IFN score (r=0.70, p<0.001) and was superior to CXCL-10 or TNF-RII in detecting the IFN signature (area under the curve (AUC) 0.86). Importantly, in patients with SLE(±APS), galectin-9 was also superior to anti-dsDNA antibody (AUC 0.70), or complement C3 (AUC 0.70) and C4 (AUC 0.78) levels in detecting the IFN signature.Galectin-9 is a novel, easy to measure hence clinically applicable biomarker to detect the IFN signature in patients with systemic autoimmune diseases such as SLE and APS.
P01.024 Corticosteroid use in elderly patients with newly diagnosed glioblastoma in the United States
Authors: F A Castro, J Davies, T Pattipaka, A Surinach, I Reyes-Rivera, J Garcia
Journal: Neuro-Oncology (2018)

Corticosteroids are widely used by patients with glioblastoma (GBM) to control oedema and radiotherapy (RT)-/chemotherapy (CT)-induced side effects. However, corticosteroid use is associated with its own potentially serious side effects. Bevacizumab (BEV) has become the current standard therapy for recurrent GBM in the USA. Clinical trials have suggested that BEV has a corticosteroid-sparing effect in patients with recurrent GBM. We aimed to evaluate this effect in elderly patients with newly diagnosed GBM treated in a real-world setting. In this retrospective, population-based study, elderly (≥66 years) patients with newly diagnosed GBM who had undergone brain surgery were identified in the SEER-Medicare database (2009–2011). Descriptive analyses were conducted to summarise corticosteroid use among BEV-treated patients by treatment period (pre-BEV period, time from diagnosis to initiation of BEV treatment; on-BEV period, time from initiation of BEV treatment until end of BEV use). Overall corticosteroid dose was reported as a median daily dose in equivalent units of dexamethasone. Corticosteroid use analyses were performed using data from BEV-treated individuals with data available in the different treatment periods. A total of 830 patients with GBM were identified, of whom 191 (23%) had been treated with BEV+RT+CT, 430 (55.7%) were treated with RT+CT, and 177 (21.3%) with RT only. Baseline characteristics: compared with RT+CT, BEV-treated patients were slightly younger (71 vs 74 years), had fewer comorbidity conditions (mean Charlson Comorbidity Index [CCI]: 0.55 vs 0.76) and a higher proportion received corticosteroids (74.9% vs 66.9%). In the BEV-treated group, a decrease in the proportion of patients using corticosteroids was observed after initiation of BEV (67.5% pre-BEV vs 51.0% on-BEV). Additionally, there was a reduction in the daily dose of corticosteroids after initiation of BEV treatment (median daily dose: 7.2 mg pre-BEV vs 2.0 mg on-BEV). Similar results were seen among individuals with data available in both the pre-BEV treatment period and the on-BEV treatment periods. The patterns of corticosteroid use in patients with GBM treated with BEV observed in this real-world study is similar to corticosteroid usage patterns reported in clinical trials, supporting a corticosteroid-sparing effect of BEV in patients with GBM.
Prognostic significance of VEGF-A expression in patients with cervical cancer.
Authors: Oleg Ivanovich Kit, Nailya Guskova, Ekaterina V. Verenikina, Ludmila Ya. Rozenko, Galina Andreevna Nerodo, Tatiana Yu. Myagkova, Khava A. Mogushkova, Ekaterina Guskova, Irina V. Tselishcheva, Anastasia Nozdricheva, Kristina Avanesova, Marina A. Gusareva, Svetlana V. Abakumova, Nadezhda Golomeeva, Izabella Torpudzhyan, Zinaida P. Lisunova, Svetlana V. Belgova, Viktoria Zakharchenko, Ineya I. Zekhtser
Journal: Journal of Clinical Oncology (2018)

e17505 Background: The purpose of the study was to determine the VEGF-A expression in patients with cervical cancer to assess its prognostic value. Methods: The study included 82 patients (23-70 years, median age 50.5±1.3 years) who underwent surgery for cervical cancer (T1aNоMo – 23 patients, T1bNоMo – 42, T2aNоMo – 17). The VEGF-А expression was determined in the blood serum before and after surgery (Elisa, Chem Well, USA). The results were compared with clinical and morphological data. The control group included 18 healthy women with similar age distribution. Results: Levels of VEGF-A in controls did not exceed 250 pg/mL, and in 16.7% were 100-150 pg/mL. The levels in cancer patients before treatment were significantly higher, on average 3547±380.0 pg/mL (p < 0.001). The expression of VEGF-A differed in dependence on the disease stage: 1000-1200 pg/mL in 52.2% (12) patients with T1aNоMo, 35.7% (15) with T1bNоMo and 23.5% (4) with T2aNоMo, and ˃2600 pg/mL in 47.8% (11), 64.3% (27) and 76.5% (13), respectively. The VEGF-A levels depended on the depth of tumor invasion and were maximal at the depth of 8-10 mm. Patients with exophytic tumors demonstrated higher levels of VEGF-A (3858.22±97.0 pg/mL), compared to patients with endophytic tumors (3030.28±85.0, p < 0.05). An analysis of the VEGF-A expression in dependence on the tumor grade showed the highest VEGF-A levels in poorly differentiated tumors (G3) – 1.5 times higher than in moderately differentiated tumors (G2, p < 0.05). The VEGF-A levels decreased after surgery in patients without lymph node metastases. Conclusions: Serum levels of VEGF-A in patients with cervical cancer depended on the growth pattern, grade and stage of tumors, demonstrating the significance of determining the VEGF-A expression in predicting a poor prognosis of cervical cancer.